7-105536594-A-T

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_021930.6(RINT1):c.118A>T(p.Ser40Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.18 in 1,598,734 control chromosomes in the GnomAD database, including 28,022 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. S40N) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.20 ( 3240 hom., cov: 32)

Exomes 𝑓: 0.18 ( 24782 hom. )

Consequence

RINT1
NM_021930.6 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: 1.44

Publications

26 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 -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0042554736).

BP6

Variant 7-105536594-A-T is Benign according to our data. Variant chr7-105536594-A-T is described in ClinVar as Benign. ClinVar VariationId is 403377.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.249 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_021930.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
RINT1	NM_021930.6	MANE Select	c.118A>T	p.Ser40Cys	missense	Exon 3 of 15	NP_068749.3
RINT1	NM_001346601.2		c.-805A>T		5_prime_UTR_premature_start_codon_gain	Exon 3 of 15	NP_001333530.1
RINT1	NM_001346600.2		c.-902A>T		5_prime_UTR_premature_start_codon_gain	Exon 3 of 15	NP_001333529.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
RINT1	ENST00000257700.7	TSL:1 MANE Select	c.118A>T	p.Ser40Cys	missense	Exon 3 of 15	ENSP00000257700.2
RINT1	ENST00000467392.5	TSL:3	n.118A>T		non_coding_transcript_exon	Exon 3 of 6	ENSP00000418805.1
RINT1	ENST00000482041.5	TSL:4	n.*112A>T		non_coding_transcript_exon	Exon 4 of 5	ENSP00000417107.1

Frequencies

GnomAD3 genomes

AF:

0.198

AC:

30179

AN:

152042

Hom.:

3230

Cov.:

show subpopulations

Gnomad AFR

AF:

0.251

Gnomad AMI

AF:

0.119

Gnomad AMR

AF:

0.177

Gnomad ASJ

AF:

0.193

Gnomad EAS

AF:

0.0227

Gnomad SAS

AF:

0.259

Gnomad FIN

AF:

0.193

Gnomad MID

AF:

0.174

Gnomad NFE

AF:

0.183

Gnomad OTH

AF:

0.185

GnomAD2 exomes

AF:

0.188

AC:

45701

AN:

243608

AF XY:

0.190

show subpopulations

Gnomad AFR exome

AF:

0.250

Gnomad AMR exome

AF:

0.202

Gnomad ASJ exome

AF:

0.192

Gnomad EAS exome

AF:

0.0232

Gnomad FIN exome

AF:

0.190

Gnomad NFE exome

AF:

0.183

Gnomad OTH exome

AF:

0.201

GnomAD4 exome

AF:

0.178

AC:

257681

AN:

1446574

Hom.:

24782

Cov.:

AF XY:

0.181

AC XY:

130294

AN XY:

719658

show subpopulations

African (AFR)

AF:

0.251

AC:

8243

AN:

32866

American (AMR)

AF:

0.198

AC:

8371

AN:

42320

Ashkenazi Jewish (ASJ)

AF:

0.190

AC:

4887

AN:

25714

East Asian (EAS)

AF:

0.0154

AC:

608

AN:

39526

South Asian (SAS)

AF:

0.249

AC:

20844

AN:

83648

European-Finnish (FIN)

AF:

0.188

AC:

10006

AN:

53202

Middle Eastern (MID)

AF:

0.220

AC:

1252

AN:

5702

European-Non Finnish (NFE)

AF:

0.174

AC:

192437

AN:

1103832

Other (OTH)

AF:

0.185

AC:

11033

AN:

59764

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.465

Heterozygous variant carriers

8592

17185

25777

34370

42962

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

6700

13400

20100

26800

33500

<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:

0.199

AC:

30229

AN:

152160

Hom.:

3240

Cov.:

AF XY:

0.199

AC XY:

14772

AN XY:

74396

show subpopulations

African (AFR)

AF:

0.251

AC:

10430

AN:

41494

American (AMR)

AF:

0.176

AC:

2693

AN:

15268

Ashkenazi Jewish (ASJ)

AF:

0.193

AC:

670

AN:

3470

East Asian (EAS)

AF:

0.0226

AC:

117

AN:

5188

South Asian (SAS)

AF:

0.261

AC:

1259

AN:

4826

European-Finnish (FIN)

AF:

0.193

AC:

2047

AN:

10592

Middle Eastern (MID)

AF:

0.173

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.183

AC:

12465

AN:

68006

Other (OTH)

AF:

0.184

AC:

389

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1224

2448

3671

4895

6119

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

332

664

996

1328

1660

<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:

0.182

Hom.:

2025

Bravo

AF:

0.199

TwinsUK

AF:

0.166

AC:

614

ALSPAC

AF:

0.173

AC:

667

ESP6500AA

AF:

0.254

AC:

1117

ESP6500EA

AF:

0.180

AC:

1548

ExAC

AF:

0.189

AC:

22915

Asia WGS

AF:

0.125

AC:

436

AN:

3478

ClinVar

ClinVar submissions as Germline

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

not specified (2)

Infantile liver failure syndrome 3 (1)

RINT1-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.072

BayesDel_addAF

Benign

-0.71

BayesDel_noAF

Benign

-0.65

CADD

Benign

(source)

DANN

Benign

0.95

DEOGEN2

Benign

0.061

Eigen

Benign

-0.62

Eigen_PC

Benign

-0.58

FATHMM_MKL

Uncertain

0.78

LIST_S2

Benign

0.35

MetaRNN

Benign

0.0043

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.90

PhyloP100

1.4

PrimateAI

Benign

0.30

PROVEAN

Benign

-0.87

REVEL

Benign

0.040

Sift

Benign

0.057

Sift4G

Benign

0.069

Polyphen

0.0

Vest4

0.029

MPC

0.18

ClinPred

0.0058

GERP RS

2.8

Varity_R

0.054

gMVP

0.13

Mutation Taster

=98/2

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

Splicevardb

2.0

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

ClinVar submissions as Germline

Computational scores

Splicing

Publications

Other links and lift over