Variant chr2-211947372-T-C 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_005235.3(ERBB4):c.421+58A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.262 in 1,355,306 control chromosomes in the GnomAD database, including 50,225 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.29 ( 6717 hom., cov: 32)

Exomes 𝑓: 0.26 ( 43508 hom. )

Consequence

ERBB4
NM_005235.3 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: -3.40

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:

ERBB4 (HGNC:):

ERBB4 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.94).

BP6

Variant 2-211947372-T-C is Benign according to our data. Variant chr2-211947372-T-C is described in ClinVar as [Benign]. Clinvar id is 1273302.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.392 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ERBB4	NM_005235.3 linkuse as main transcript	c.421+58A>G		intron_variant		ENST00000342788.9	NP_005226.1	Q15303-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ERBB4	ENST00000342788.9 linkuse as main transcript	c.421+58A>G		intron_variant		1	NM_005235.3	ENSP00000342235.4		Q15303-1

Frequencies

GnomAD3 genomes

AF:

0.288

AC:

43821

AN:

152016

Hom.:

6697

Cov.:

show subpopulations

Gnomad AFR

AF:

0.351

Gnomad AMI

AF:

0.201

Gnomad AMR

AF:

0.349

Gnomad ASJ

AF:

0.378

Gnomad EAS

AF:

0.393

Gnomad SAS

AF:

0.405

Gnomad FIN

AF:

0.220

Gnomad MID

AF:

0.335

Gnomad NFE

AF:

0.227

Gnomad OTH

AF:

0.306

GnomAD4 exome

AF:

0.259

AC:

311854

AN:

1203172

Hom.:

43508

AF XY:

0.263

AC XY:

160791

AN XY:

611370

show subpopulations

Gnomad4 AFR exome

AF:

0.359

Gnomad4 AMR exome

AF:

0.405

Gnomad4 ASJ exome

AF:

0.351

Gnomad4 EAS exome

AF:

0.394

Gnomad4 SAS exome

AF:

0.414

Gnomad4 FIN exome

AF:

0.220

Gnomad4 NFE exome

AF:

0.227

Gnomad4 OTH exome

AF:

0.270

GnomAD4 genome

AF:

0.288

AC:

43878

AN:

152134

Hom.:

6717

Cov.:

AF XY:

0.292

AC XY:

21754

AN XY:

74376

show subpopulations

Gnomad4 AFR

AF:

0.351

Gnomad4 AMR

AF:

0.350

Gnomad4 ASJ

AF:

0.378

Gnomad4 EAS

AF:

0.393

Gnomad4 SAS

AF:

0.407

Gnomad4 FIN

AF:

0.220

Gnomad4 NFE

AF:

0.227

Gnomad4 OTH

AF:

0.304

Alfa

AF:

0.256

Hom.:

651

Bravo

AF:

0.301

Asia WGS

AF:

0.392

AC:

1363

AN:

3478

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	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	May 11, 2021	- -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan

Jul 15, 2024

This variant is classified as Benign based on local population frequency. This variant was detected in 38% of patients studied in a panel designed for Epileptic and Developmental Encephalopathy and Progressive Myoclonus Epilepsy. Number of patients: 35. Only high quality variants are reported. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.94

CADD

Benign

0.049

DANN

Benign

0.51

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