chr7-105542599-C-T

Variant names:

Variant summary

Our verdict is Benign. The variant received -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BS1BS2

The NM_021930.6(RINT1):c.465C>T(p.Ile155Ile) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00486 in 1,613,976 control chromosomes in the GnomAD database, including 128 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0063 ( 16 hom., cov: 31)

Exomes 𝑓: 0.0047 ( 112 hom. )

Consequence

RINT1
NM_021930.6 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.370

Publications

2 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 -19 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.3).

BP6

Variant 7-105542599-C-T is Benign according to our data. Variant chr7-105542599-C-T is described in ClinVar as Benign. ClinVar VariationId is 416394.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-0.37 with no splicing effect.

BS1

Variant frequency is greater than expected in population eas. GnomAd4 allele frequency = 0.0063 (959/152202) while in subpopulation EAS AF = 0.0353 (183/5186). AF 95% confidence interval is 0.0311. There are 16 homozygotes in GnomAd4. There are 564 alleles in the male GnomAd4 subpopulation. Median coverage is 31. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 16 AR,AD gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RINT1	NM_021930.6 link	c.465C>T	p.Ile155Ile	synonymous_variant	Exon 4 of 15	ENST00000257700.7	NP_068749.3	Q6NUQ1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RINT1	ENST00000257700.7 link	c.465C>T	p.Ile155Ile	synonymous_variant	Exon 4 of 15	1	NM_021930.6	ENSP00000257700.2		Q6NUQ1

Frequencies

GnomAD3 genomes

AF:

0.00631

AC:

959

AN:

152086

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00360

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0135

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.0356

Gnomad SAS

AF:

0.00414

Gnomad FIN

AF:

0.0238

Gnomad MID

AF:

0.00318

Gnomad NFE

AF:

0.00200

Gnomad OTH

AF:

0.00478

GnomAD2 exomes

AF:

0.0104

AC:

2605

AN:

251328

AF XY:

0.00922

show subpopulations

Gnomad AFR exome

AF:

0.00338

Gnomad AMR exome

AF:

0.0325

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0294

Gnomad FIN exome

AF:

0.0222

Gnomad NFE exome

AF:

0.00230

Gnomad OTH exome

AF:

0.00913

GnomAD4 exome

AF:

0.00471

AC:

6887

AN:

1461774

Hom.:

112

Cov.:

AF XY:

0.00454

AC XY:

3298

AN XY:

727184

show subpopulations

African (AFR)

AF:

0.00346

AC:

116

AN:

33478

American (AMR)

AF:

0.0302

AC:

1350

AN:

44704

Ashkenazi Jewish (ASJ)

AF:

0.0000765

AC:

AN:

26134

East Asian (EAS)

AF:

0.0490

AC:

1944

AN:

39698

South Asian (SAS)

AF:

0.00237

AC:

204

AN:

86222

European-Finnish (FIN)

AF:

0.0209

AC:

1117

AN:

53418

Middle Eastern (MID)

AF:

0.00191

AC:

AN:

5766

European-Non Finnish (NFE)

AF:

0.00163

AC:

1818

AN:

1111964

Other (OTH)

AF:

0.00538

AC:

325

AN:

60390

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.492

Heterozygous variant carriers

376

752

1127

1503

1879

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

106

212

318

424

530

<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:

0.00630

AC:

959

AN:

152202

Hom.:

Cov.:

AF XY:

0.00758

AC XY:

564

AN XY:

74436

show subpopulations

African (AFR)

AF:

0.00361

AC:

150

AN:

41542

American (AMR)

AF:

0.0136

AC:

208

AN:

15270

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.0353

AC:

183

AN:

5186

South Asian (SAS)

AF:

0.00415

AC:

AN:

4822

European-Finnish (FIN)

AF:

0.0238

AC:

252

AN:

10598

Middle Eastern (MID)

AF:

0.00

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.00200

AC:

136

AN:

67994

Other (OTH)

AF:

0.00473

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

136

181

226

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

100

<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:

0.00251

Hom.:

Bravo

AF:

0.00591

Asia WGS

AF:

0.0230

AC:

AN:

3478

EpiCase

AF:

0.00125

EpiControl

AF:

0.00148

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

- -

Jan 28, 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

Mar 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

-0.30

CADD

Benign

6.3

(source)

DANN

Benign

0.72

PhyloP100

-0.37

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Mutation Taster

=99/1

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

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