Variant rs2230698 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_StrongBP6_ModerateBP7BA1

The NM_004448.4(ERBB2):c.1371A>G(p.Ser457=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00725 in 1,609,958 control chromosomes in the GnomAD database, including 692 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.037 ( 356 hom., cov: 32)

Exomes 𝑓: 0.0041 ( 336 hom. )

Consequence

ERBB2
NM_004448.4 synonymous

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -4.03

Variant links:

Genes affected

ERBB2 (HGNC:3430): (erb-b2 receptor tyrosine kinase 2) This gene encodes a member of the epidermal growth factor (EGF) receptor family of receptor tyrosine kinases. This protein has no ligand binding domain of its own and therefore cannot bind growth factors. However, it does bind tightly to other ligand-bound EGF receptor family members to form a heterodimer, stabilizing ligand binding and enhancing kinase-mediated activation of downstream signalling pathways, such as those involving mitogen-activated protein kinase and phosphatidylinositol-3 kinase. Allelic variations at amino acid positions 654 and 655 of isoform a (positions 624 and 625 of isoform b) have been reported, with the most common allele, Ile654/Ile655, shown here. Amplification and/or overexpression of this gene has been reported in numerous cancers, including breast and ovarian tumors. Alternative splicing results in several additional transcript variants, some encoding different isoforms and others that have not been fully characterized. [provided by RefSeq, Jul 2008]

ERBB2 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -15 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.89).

BP6

Variant 17-39715797-A-G is Benign according to our data. Variant chr17-39715797-A-G is described in ClinVar as [Benign]. Clinvar id is 1168005.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=-4.03 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.124 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ERBB2	NM_004448.4 linkuse as main transcript	c.1371A>G	p.Ser457=	synonymous_variant	12/27	ENST00000269571.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ERBB2	ENST00000269571.10 linkuse as main transcript	c.1371A>G	p.Ser457=	synonymous_variant	12/27	1	NM_004448.4	P1	P04626-1

Frequencies

GnomAD3 genomes

AF:

0.0369

AC:

5611

AN:

152146

Hom.:

356

Cov.:

show subpopulations

Gnomad AFR

AF:

0.127

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0170

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000192

Gnomad SAS

AF:

0.00104

Gnomad FIN

AF:

0.000565

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.000691

Gnomad OTH

AF:

0.0225

GnomAD3 exomes

AF:

0.0113

AC:

2814

AN:

248042

Hom.:

146

AF XY:

0.00832

AC XY:

1118

AN XY:

134428

show subpopulations

Gnomad AFR exome

AF:

0.136

Gnomad AMR exome

AF:

0.0147

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000109

Gnomad SAS exome

AF:

0.000457

Gnomad FIN exome

AF:

0.000435

Gnomad NFE exome

AF:

0.000396

Gnomad OTH exome

AF:

0.00524

GnomAD4 exome

AF:

0.00415

AC:

6049

AN:

1457694

Hom.:

336

Cov.:

AF XY:

0.00353

AC XY:

2561

AN XY:

725452

show subpopulations

Gnomad4 AFR exome

AF:

0.133

Gnomad4 AMR exome

AF:

0.0142

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000101

Gnomad4 SAS exome

AF:

0.000522

Gnomad4 FIN exome

AF:

0.000588

Gnomad4 NFE exome

AF:

0.000269

Gnomad4 OTH exome

AF:

0.00909

GnomAD4 genome

AF:

0.0370

AC:

5627

AN:

152264

Hom.:

356

Cov.:

AF XY:

0.0356

AC XY:

2647

AN XY:

74454

show subpopulations

Gnomad4 AFR

AF:

0.127

Gnomad4 AMR

AF:

0.0169

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.00104

Gnomad4 FIN

AF:

0.000565

Gnomad4 NFE

AF:

0.000691

Gnomad4 OTH

AF:

0.0242

Alfa

AF:

0.0192

Hom.:

Bravo

AF:

0.0427

Asia WGS

AF:

0.0170

AC:

AN:

3478

EpiCase

AF:

0.000327

EpiControl

AF:

0.000356

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Feb 01, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.89

CADD

Benign

0.094

DANN

Benign

0.41

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