Variant chr5-66025483-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -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. 13/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another nucleotide change resulting in the same amino acid substitution has been previously reported as Likely benign in UniProt.

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

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 made for transcript

Verdict is Benign. Variant got -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/exons	MANE	Protein	UniProt
ERBIN	NM_001253697.2 link	c.821C>T	p.Ser274Leu	missense_variant	11/26	ENST00000284037.10	NP_001240626.1	Q96RT1-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ERBIN	ENST00000284037.10 link	c.821C>T	p.Ser274Leu	missense_variant	11/26	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

GnomAD3 exomes

AF:

0.153

AC:

38297

AN:

250684

Hom.:

3343

AF XY:

0.158

AC XY:

21414

AN XY:

135592

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 SAS exome

AF:

0.241

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

Gnomad4 AFR exome

AF:

0.0239

Gnomad4 AMR exome

AF:

0.161

Gnomad4 ASJ exome

AF:

0.104

Gnomad4 EAS exome

AF:

0.0886

Gnomad4 SAS exome

AF:

0.235

Gnomad4 FIN exome

AF:

0.159

Gnomad4 NFE exome

AF:

0.156

Gnomad4 OTH exome

AF:

0.142

GnomAD4 genome

AF:

0.120

AC:

18249

AN:

151792

Hom.:

1411

Cov.:

AF XY:

0.121

AC XY:

9004

AN XY:

74180

show subpopulations

Gnomad4 AFR

AF:

0.0308

Gnomad4 AMR

AF:

0.146

Gnomad4 ASJ

AF:

0.0967

Gnomad4 EAS

AF:

0.0959

Gnomad4 SAS

AF:

0.243

Gnomad4 FIN

AF:

0.151

Gnomad4 NFE

AF:

0.157

Gnomad4 OTH

AF:

0.105

Alfa

AF:

0.146

Hom.:

4106

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

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Feb 01, 2024	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan

Jan 24, 2024

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

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

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

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over