rs13393577

chr2-212432139-T-C

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_005235.3(ERBB4):c.82+106310A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.103 in 152,228 control chromosomes in the GnomAD database, including 868 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.10 (868 hom., cov: 32)
• Consequence: ERBB4 NM_005235.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.15

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]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BP6: Variant 2-212432139-T-C is Benign according to our data. Variant chr2-212432139-T-C is described in ClinVar as [Benign]. Clinvar id is 1598694.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.128 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ERBB4	NM_005235.3	c.82+106310A>G		intron_variant		ENST00000342788.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ERBB4	ENST00000342788.9	c.82+106310A>G		intron_variant		1	NM_005235.3	P4
ERBB4	ENST00000436443.5	c.82+106310A>G		intron_variant		1		A1
ERBB4	ENST00000484594.5	n.134+106310A>G		intron_variant, non_coding_transcript_variant		1
ERBB4	ENST00000260943.11	c.82+106310A>G		intron_variant		5

Frequencies

GnomAD3 genomes AF: 0.103 AC: 15723 AN: 152110 Hom.: 861 Cov.: 32

Gnomad AFR AF: 0.130

Gnomad AMI AF: 0.0252

Gnomad AMR AF: 0.0967

Gnomad ASJ AF: 0.0568

Gnomad EAS AF: 0.0491

Gnomad SAS AF: 0.136

Gnomad FIN AF: 0.127

Gnomad MID AF: 0.0475

Gnomad NFE AF: 0.0906

Gnomad OTH AF: 0.0946

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.103 AC: 15755 AN: 152228 Hom.: 868 Cov.: 32 AF XY: 0.104 AC XY: 7750 AN XY: 74434

Gnomad4 AFR AF: 0.130

Gnomad4 AMR AF: 0.0970

Gnomad4 ASJ AF: 0.0568

Gnomad4 EAS AF: 0.0492

Gnomad4 SAS AF: 0.136

Gnomad4 FIN AF: 0.127

Gnomad4 NFE AF: 0.0906

Gnomad4 OTH AF: 0.0936

Alfa AF: 0.0892 Hom.: 823

Bravo AF: 0.103

Asia WGS AF: 0.115 AC: 400 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jan 08, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
Cadd	Benign	14
Dann	Benign	0.60

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.080		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

Other links and lift over

dbSNP: rs13393577; hg19: chr2-213296863; COSMIC: COSV53504887; COSMIC: COSV53504887;