rs113947297

Variant names:

Variant summary

Our verdict is Benign. The variant received -18 ACMG points: 0P and 18B. BP4_ModerateBP6_Very_StrongBS1BS2

The NM_021930.6(RINT1):c.840-5G>A variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0321 in 1,613,462 control chromosomes in the GnomAD database, including 1,149 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.026 ( 115 hom., cov: 32)

Exomes 𝑓: 0.033 ( 1034 hom. )

Consequence

RINT1
NM_021930.6 splice_region, intron

Scores

Splicing: ADA: 0.0004732

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: 0.588

Publications

6 publications found

Variant links:

Genes affected

RINT1 (HGNC:21876): (RAD50 interactor 1) This gene encodes a protein first identified for its ability to interact with the RAD50 double strand break repair protein, with the resulting interaction implicated in the regulation of cell cycle progression and telomere length. The encoded protein may also play a role in trafficking of cellular cargo from the endosome to the trans-Golgi network. Mutations in this gene may be associated with breast cancer in human patients. [provided by RefSeq, Oct 2016]

RINT1 Gene-Disease associations (from GenCC):

infantile liver failure syndrome 3
Inheritance: AR Classification: STRONG, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), G2P, Ambry Genetics
infantile liver failure syndrome 2
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
breast cancer
Inheritance: AD Classification: NO_KNOWN Submitted by: Ambry Genetics
familial ovarian cancer
Inheritance: AD Classification: NO_KNOWN Submitted by: ClinGen
hereditary breast carcinoma
Inheritance: AD Classification: NO_KNOWN Submitted by: ClinGen

RINT1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -18 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.36).

BP6

Variant 7-105548549-G-A is Benign according to our data. Variant chr7-105548549-G-A is described in ClinVar as Benign. ClinVar VariationId is 416378.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.0264 (4011/152166) while in subpopulation NFE AF = 0.0381 (2594/67998). AF 95% confidence interval is 0.0369. There are 115 homozygotes in GnomAd4. There are 1992 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 115 AR,AD gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RINT1	NM_021930.6 link	c.840-5G>A		splice_region_variant, intron_variant	Intron 6 of 14	ENST00000257700.7	NP_068749.3	Q6NUQ1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RINT1	ENST00000257700.7 link	c.840-5G>A		splice_region_variant, intron_variant	Intron 6 of 14	1	NM_021930.6	ENSP00000257700.2		Q6NUQ1
RINT1	ENST00000497979.5 link	n.*445-5G>A		splice_region_variant, intron_variant	Intron 6 of 14	5		ENSP00000420582.1		F8WDC5

Frequencies

GnomAD3 genomes

AF:

0.0264

AC:

4011

AN:

152048

Hom.:

115

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00654

Gnomad AMI

AF:

0.0758

Gnomad AMR

AF:

0.00944

Gnomad ASJ

AF:

0.00894

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00269

Gnomad FIN

AF:

0.0805

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.0381

Gnomad OTH

AF:

0.0168

GnomAD2 exomes

AF:

0.0264

AC:

6645

AN:

251414

AF XY:

0.0261

show subpopulations

Gnomad AFR exome

AF:

0.00486

Gnomad AMR exome

AF:

0.00610

Gnomad ASJ exome

AF:

0.00754

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0804

Gnomad NFE exome

AF:

0.0377

Gnomad OTH exome

AF:

0.0274

GnomAD4 exome

AF:

0.0327

AC:

47835

AN:

1461296

Hom.:

1034

Cov.:

AF XY:

0.0319

AC XY:

23203

AN XY:

726964

show subpopulations

African (AFR)

AF:

0.00454

AC:

152

AN:

33470

American (AMR)

AF:

0.00695

AC:

311

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.00796

AC:

208

AN:

26126

East Asian (EAS)

AF:

0.0000252

AC:

AN:

39688

South Asian (SAS)

AF:

0.00310

AC:

267

AN:

86256

European-Finnish (FIN)

AF:

0.0847

AC:

4524

AN:

53404

Middle Eastern (MID)

AF:

0.0146

AC:

AN:

5766

European-Non Finnish (NFE)

AF:

0.0364

AC:

40500

AN:

1111480

Other (OTH)

AF:

0.0296

AC:

1788

AN:

60382

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.465

Heterozygous variant carriers

2051

4102

6154

8205

10256

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

1440

2880

4320

5760

7200

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0264

AC:

4011

AN:

152166

Hom.:

115

Cov.:

AF XY:

0.0268

AC XY:

1992

AN XY:

74374

show subpopulations

African (AFR)

AF:

0.00653

AC:

271

AN:

41528

American (AMR)

AF:

0.00943

AC:

144

AN:

15278

Ashkenazi Jewish (ASJ)

AF:

0.00894

AC:

AN:

3468

East Asian (EAS)

AF:

0.00

AC:

AN:

5178

South Asian (SAS)

AF:

0.00270

AC:

AN:

4820

European-Finnish (FIN)

AF:

0.0805

AC:

852

AN:

10584

Middle Eastern (MID)

AF:

0.00680

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0381

AC:

2594

AN:

67998

Other (OTH)

AF:

0.0166

AC:

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

200

400

600

800

1000

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

138

184

230

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0337

Hom.:

197

Bravo

AF:

0.0206

Asia WGS

AF:

0.00260

AC:

AN:

3478

EpiCase

AF:

0.0291

EpiControl

AF:

0.0289

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Feb 02, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not specified

Benign:1

Jul 30, 2020

Ambry Genetics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This alteration is classified as benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

RINT1-related disorder

Benign:1

Oct 28, 2019

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.36

CADD

Benign

(source)

DANN

Benign

0.70

PhyloP100

0.59

Mutation Taster

=84/16

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.00047

dbscSNV1_RF

Benign

0.062

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over