chr2-211387139-T-C

Variant names:

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_005235.3(ERBB4):c.3195A>G(p.Val1065Val) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.32 in 1,610,022 control chromosomes in the GnomAD database, including 85,843 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.26 ( 6088 hom., cov: 32)

Exomes 𝑓: 0.33 ( 79755 hom. )

Consequence

ERBB4
NM_005235.3 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: -1.59

Variant links:

Genes affected

ERBB4 (HGNC:3432): (erb-b2 receptor tyrosine kinase 4) This gene is a member of the Tyr protein kinase family and the epidermal growth factor receptor subfamily. It encodes a single-pass type I membrane protein with multiple cysteine rich domains, a transmembrane domain, a tyrosine kinase domain, a phosphotidylinositol-3 kinase binding site and a PDZ domain binding motif. The protein binds to and is activated by neuregulins and other factors and induces a variety of cellular responses including mitogenesis and differentiation. Multiple proteolytic events allow for the release of a cytoplasmic fragment and an extracellular fragment. Mutations in this gene have been associated with cancer. Alternatively spliced variants which encode different protein isoforms have been described; however, not all variants have been fully characterized. [provided by RefSeq, Jul 2008]

ERBB4 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.83).

BP6

Variant 2-211387139-T-C is Benign according to our data. Variant chr2-211387139-T-C is described in ClinVar as [Benign]. Clinvar id is 1210024.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-211387139-T-C is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=-1.59 with no splicing effect.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.334 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ERBB4	NM_005235.3 link	c.3195A>G	p.Val1065Val	synonymous_variant	Exon 27 of 28	ENST00000342788.9	NP_005226.1	Q15303-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
ERBB4	ENST00000342788.9 link	c.3195A>G	p.Val1065Val	synonymous_variant	Exon 27 of 28	1	NM_005235.3	ENSP00000342235.4	Q15303-1
ERBB4	ENST00000436443.5 link	c.3147A>G	p.Val1049Val	synonymous_variant	Exon 26 of 27	1		ENSP00000403204.1	Q15303-3
ERBB4	ENST00000260943.11 link	c.3117A>G	p.Val1039Val	synonymous_variant	Exon 26 of 27	5		ENSP00000260943.7	Q15303-4H3BLT0

Frequencies

GnomAD3 genomes

AF:

0.261

AC:

39631

AN:

151972

Hom.:

6091

Cov.:

show subpopulations

Gnomad AFR

AF:

0.100

Gnomad AMI

AF:

0.287

Gnomad AMR

AF:

0.255

Gnomad ASJ

AF:

0.331

Gnomad EAS

AF:

0.311

Gnomad SAS

AF:

0.259

Gnomad FIN

AF:

0.352

Gnomad MID

AF:

0.282

Gnomad NFE

AF:

0.338

Gnomad OTH

AF:

0.267

GnomAD3 exomes

AF:

0.300

AC:

75209

AN:

250482

Hom.:

12070

AF XY:

0.304

AC XY:

41161

AN XY:

135438

show subpopulations

Gnomad AFR exome

AF:

0.0918

Gnomad AMR exome

AF:

0.260

Gnomad ASJ exome

AF:

0.328

Gnomad EAS exome

AF:

0.311

Gnomad SAS exome

AF:

0.263

Gnomad FIN exome

AF:

0.352

Gnomad NFE exome

AF:

0.338

Gnomad OTH exome

AF:

0.306

GnomAD4 exome

AF:

0.326

AC:

475578

AN:

1457930

Hom.:

79755

Cov.:

AF XY:

0.326

AC XY:

236382

AN XY:

725530

show subpopulations

Gnomad4 AFR exome

AF:

0.0876

Gnomad4 AMR exome

AF:

0.260

Gnomad4 ASJ exome

AF:

0.330

Gnomad4 EAS exome

AF:

0.276

Gnomad4 SAS exome

AF:

0.265

Gnomad4 FIN exome

AF:

0.354

Gnomad4 NFE exome

AF:

0.342

Gnomad4 OTH exome

AF:

0.315

GnomAD4 genome

AF:

0.261

AC:

39628

AN:

152092

Hom.:

6088

Cov.:

AF XY:

0.260

AC XY:

19312

AN XY:

74336

show subpopulations

Gnomad4 AFR

AF:

0.0999

Gnomad4 AMR

AF:

0.255

Gnomad4 ASJ

AF:

0.331

Gnomad4 EAS

AF:

0.312

Gnomad4 SAS

AF:

0.258

Gnomad4 FIN

AF:

0.352

Gnomad4 NFE

AF:

0.338

Gnomad4 OTH

AF:

0.265

Alfa

AF:

0.312

Hom.:

10564

Bravo

AF:

0.247

Asia WGS

AF:

0.238

AC:

827

AN:

3478

EpiCase

AF:

0.323

EpiControl

AF:

0.330

ClinVar

Significance: Benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:3

Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Genome Diagnostics Laboratory, Amsterdam University Medical Center

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Jul 15, 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 40% of patients studied in a panel designed for Epileptic and Developmental Encephalopathy and Progressive Myoclonus Epilepsy. Number of patients: 37. Only high quality variants are reported. -

not provided

Benign:3

Feb 04, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Jun 25, 2020

GeneDx

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

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.83

CADD

Benign

0.53

DANN

Benign

0.48

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