Variant chr17-39699581-C-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The ENST00000578199.5(ERBB2):c.-18+4400C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.119 in 1,516,162 control chromosomes in the GnomAD database, including 12,340 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as not provided (no stars).

Frequency

Genomes: 𝑓 0.087 ( 821 hom., cov: 32)

Exomes 𝑓: 0.12 ( 11519 hom. )

Consequence

ERBB2
ENST00000578199.5 intron

Scores

Clinical Significance

not provided no classification provided O:1

Conservation

PhyloP100: -0.0150

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.001347214).

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.169 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons
ERBB2	NM_001289936.2 linkuse as main transcript	c.22C>A	p.Pro8Thr	missense_variant	5/31
ERBB2	XM_047435590.1 linkuse as main transcript	c.22C>A	p.Pro8Thr	missense_variant	6/32
ERBB2	NM_001005862.3 linkuse as main transcript	c.-18+4400C>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	UniProt
ERBB2	ENST00000578199.5 linkuse as main transcript	c.-18+4400C>A		intron_variant		1
ERBB2	ENST00000541774.5 linkuse as main transcript	c.22C>A	p.Pro8Thr	missense_variant	1/27	5	P04626-4
ERBB2	ENST00000584601.5 linkuse as main transcript	c.-24C>A		5_prime_UTR_variant	5/31	2	P04626-5
ERBB2	ENST00000406381.6 linkuse as main transcript	c.-18+4400C>A		intron_variant		5	P04626-5

Frequencies

GnomAD3 genomes

AF:

0.0873

AC:

13284

AN:

152102

Hom.:

821

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0214

Gnomad AMI

AF:

0.0340

Gnomad AMR

AF:

0.0632

Gnomad ASJ

AF:

0.170

Gnomad EAS

AF:

0.00192

Gnomad SAS

AF:

0.178

Gnomad FIN

AF:

0.0680

Gnomad MID

AF:

0.123

Gnomad NFE

AF:

0.133

Gnomad OTH

AF:

0.0766

GnomAD3 exomes

AF:

0.108

AC:

13903

AN:

128144

Hom.:

1054

AF XY:

0.120

AC XY:

8421

AN XY:

70196

show subpopulations

Gnomad AFR exome

AF:

0.0199

Gnomad AMR exome

AF:

0.0427

Gnomad ASJ exome

AF:

0.167

Gnomad EAS exome

AF:

0.000767

Gnomad SAS exome

AF:

0.193

Gnomad FIN exome

AF:

0.0663

Gnomad NFE exome

AF:

0.132

Gnomad OTH exome

AF:

0.108

GnomAD4 exome

AF:

0.123

AC:

167613

AN:

1363942

Hom.:

11519

Cov.:

AF XY:

0.126

AC XY:

85144

AN XY:

674070

show subpopulations

Gnomad4 AFR exome

AF:

0.0181

Gnomad4 AMR exome

AF:

0.0473

Gnomad4 ASJ exome

AF:

0.170

Gnomad4 EAS exome

AF:

0.000616

Gnomad4 SAS exome

AF:

0.195

Gnomad4 FIN exome

AF:

0.0731

Gnomad4 NFE exome

AF:

0.128

Gnomad4 OTH exome

AF:

0.119

GnomAD4 genome

AF:

0.0872

AC:

13280

AN:

152220

Hom.:

821

Cov.:

AF XY:

0.0835

AC XY:

6215

AN XY:

74418

show subpopulations

Gnomad4 AFR

AF:

0.0213

Gnomad4 AMR

AF:

0.0631

Gnomad4 ASJ

AF:

0.170

Gnomad4 EAS

AF:

0.00193

Gnomad4 SAS

AF:

0.179

Gnomad4 FIN

AF:

0.0680

Gnomad4 NFE

AF:

0.133

Gnomad4 OTH

AF:

0.0758

Alfa

AF:

0.124

Hom.:

1345

Bravo

AF:

0.0801

TwinsUK

AF:

0.121

AC:

448

ALSPAC

AF:

0.127

AC:

489

ExAC

AF:

0.143

AC:

2006

Asia WGS

AF:

0.0630

AC:

224

AN:

3478

ClinVar

Significance: not provided

Submissions summary: Other:1

Revision: no classification provided

LINK: link

Submissions by phenotype

not specified

Other:1

not provided, no classification provided

reference population

ITMI

Sep 19, 2013

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.70

BayesDel_noAF

Benign

-0.64

CADD

Benign

3.2

DANN

Benign

0.87

Eigen

Benign

-1.0

Eigen_PC

Benign

-1.1

FATHMM_MKL

Benign

0.051

LIST_S2

Benign

0.35

MetaRNN

Benign

0.0013

MetaSVM

Benign

-1.1

MutationTaster

Benign

1.0

P;P;P;P

PROVEAN

Benign

0.61

REVEL

Benign

0.071

Sift

Benign

0.81

Sift4G

Benign

0.46

Polyphen

0.0

Vest4

0.039

ClinPred

0.0063

GERP RS

-2.2

Splicing

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