rs3213837

Variant names:

Variant summary

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

The NM_001253697.2(ERBIN):c.821C>T(p.Ser274Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.151 in 1,602,994 control chromosomes in the GnomAD database, including 19,931 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Synonymous variant affecting the same amino acid position (i.e. S274S) has been classified as Benign.

Frequency

Genomes: 𝑓 0.12 ( 1411 hom., cov: 32)

Exomes 𝑓: 0.15 ( 18520 hom. )

Consequence

ERBIN
NM_001253697.2 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 1.29

Publications

30 publications found

Variant links:

Genes affected

ERBIN (HGNC:15842): (erbb2 interacting protein) This gene is a member of the leucine-rich repeat and PDZ domain (LAP) family. The encoded protein contains 17 leucine-rich repeats and one PDZ domain. It binds to the unphosphorylated form of the ERBB2 protein and regulates ERBB2 function and localization. It has also been shown to affect the Ras signaling pathway by disrupting Ras-Raf interaction. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene. [provided by RefSeq, Nov 2011]

ERBIN 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=0.0015951693).

BP6

Variant 5-66025483-C-T is Benign according to our data. Variant chr5-66025483-C-T is described in ClinVar as [Benign]. Clinvar id is 1165181.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.231 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ERBIN	NM_001253697.2 link	c.821C>T	p.Ser274Leu	missense_variant	Exon 11 of 26	ENST00000284037.10	NP_001240626.1	Q96RT1-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ERBIN	ENST00000284037.10 link	c.821C>T	p.Ser274Leu	missense_variant	Exon 11 of 26	1	NM_001253697.2	ENSP00000284037.4		Q96RT1-1

Frequencies

GnomAD3 genomes

AF:

0.120

AC:

18257

AN:

151674

Hom.:

1414

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0309

Gnomad AMI

AF:

0.312

Gnomad AMR

AF:

0.147

Gnomad ASJ

AF:

0.0967

Gnomad EAS

AF:

0.0960

Gnomad SAS

AF:

0.243

Gnomad FIN

AF:

0.151

Gnomad MID

AF:

0.104

Gnomad NFE

AF:

0.157

Gnomad OTH

AF:

0.107

GnomAD2 exomes

AF:

0.153

AC:

38297

AN:

250684

AF XY:

0.158

show subpopulations

Gnomad AFR exome

AF:

0.0265

Gnomad AMR exome

AF:

0.162

Gnomad ASJ exome

AF:

0.107

Gnomad EAS exome

AF:

0.0948

Gnomad FIN exome

AF:

0.156

Gnomad NFE exome

AF:

0.157

Gnomad OTH exome

AF:

0.159

GnomAD4 exome

AF:

0.154

AC:

223650

AN:

1451202

Hom.:

18520

Cov.:

AF XY:

0.157

AC XY:

113606

AN XY:

722652

show subpopulations

African (AFR)

AF:

0.0239

AC:

799

AN:

33366

American (AMR)

AF:

0.161

AC:

7165

AN:

44634

Ashkenazi Jewish (ASJ)

AF:

0.104

AC:

2708

AN:

26060

East Asian (EAS)

AF:

0.0886

AC:

3501

AN:

39518

South Asian (SAS)

AF:

0.235

AC:

20156

AN:

85864

European-Finnish (FIN)

AF:

0.159

AC:

8452

AN:

53136

Middle Eastern (MID)

AF:

0.0968

AC:

551

AN:

5692

European-Non Finnish (NFE)

AF:

0.156

AC:

171779

AN:

1102922

Other (OTH)

AF:

0.142

AC:

8539

AN:

60010

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.443

Heterozygous variant carriers

8502

17005

25507

34010

42512

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.120

AC:

18249

AN:

151792

Hom.:

1411

Cov.:

AF XY:

0.121

AC XY:

9004

AN XY:

74180

show subpopulations

African (AFR)

AF:

0.0308

AC:

1279

AN:

41488

American (AMR)

AF:

0.146

AC:

2234

AN:

15256

Ashkenazi Jewish (ASJ)

AF:

0.0967

AC:

335

AN:

3464

East Asian (EAS)

AF:

0.0959

AC:

496

AN:

5174

South Asian (SAS)

AF:

0.243

AC:

1168

AN:

4812

European-Finnish (FIN)

AF:

0.151

AC:

1587

AN:

10532

Middle Eastern (MID)

AF:

0.109

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.157

AC:

10613

AN:

67758

Other (OTH)

AF:

0.105

AC:

222

AN:

2106

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

804

1609

2413

3218

4022

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.141

Hom.:

5383

Bravo

AF:

0.113

TwinsUK

AF:

0.154

AC:

571

ALSPAC

AF:

0.162

AC:

624

ESP6500AA

AF:

0.0350

AC:

154

ESP6500EA

AF:

0.156

AC:

1344

ExAC

AF:

0.154

AC:

18754

Asia WGS

AF:

0.180

AC:

627

AN:

3476

EpiCase

AF:

0.147

EpiControl

AF:

0.144

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

not specified

Benign:1

Jan 24, 2024

Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant is classified as Benign based on local population frequency. This variant was detected in 31% of patients studied by a panel of primary immunodeficiencies. Number of patients: 27. Only high quality variants are reported. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.075

BayesDel_addAF

Benign

-0.69

BayesDel_noAF

Benign

-0.61

CADD

Benign

(source)

DANN

Benign

0.84

DEOGEN2

Benign

0.036

T;.;T;.;.;.;.;.

Eigen

Benign

-0.72

Eigen_PC

Benign

-0.60

FATHMM_MKL

Benign

0.37

LIST_S2

Uncertain

0.87

D;D;D;D;D;D;D;.

MetaRNN

Benign

0.0016

T;T;T;T;T;T;T;T

MetaSVM

Benign

-1.0

PhyloP100

1.3

PrimateAI

Benign

0.46

PROVEAN

Benign

-0.85

N;N;N;N;N;N;N;N

REVEL

Benign

0.034

Sift

Benign

0.55

T;T;T;T;T;T;T;T

Sift4G

Benign

0.81

T;T;T;T;T;T;T;T

Polyphen

0.0010

B;B;B;B;B;.;.;B

Vest4

0.12

MPC

0.061

ClinPred

0.0042

GERP RS

2.3

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.056

gMVP

0.40

Mutation Taster

=97/3

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

rs3213837

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