2-211721519-C-T

Variant names:

• chr2-211721519-C-T
• rs4673629
• NM_005235.3:c.883+874G>A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_005235.3(ERBB4):​c.883+874G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.573 in 141,074 control chromosomes in the GnomAD database, including 24,117 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.57 (24117 hom., cov: 21)
• Consequence: ERBB4 NM_005235.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.379

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.0).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.727 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ERBB4	NM_005235.3	c.883+874G>A		intron_variant	Intron 7 of 27	ENST00000342788.9	NP_005226.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ERBB4	ENST00000342788.9	c.883+874G>A		intron_variant	Intron 7 of 27	1	NM_005235.3	ENSP00000342235.4
ERBB4	ENST00000436443.5	c.883+874G>A		intron_variant	Intron 7 of 26	1		ENSP00000403204.1
ERBB4	ENST00000484594.5	n.935+874G>A		intron_variant	Intron 7 of 19	1
ERBB4	ENST00000260943.11	c.883+874G>A		intron_variant	Intron 7 of 26	5		ENSP00000260943.7

Frequencies

GnomAD3 genomes AF: 0.573 AC: 80877 AN: 141056 Hom.: 24107 Cov.: 21

Gnomad AFR AF: 0.735

Gnomad AMI AF: 0.363

Gnomad AMR AF: 0.593

Gnomad ASJ AF: 0.308

Gnomad EAS AF: 0.479

Gnomad SAS AF: 0.628

Gnomad FIN AF: 0.584

Gnomad MID AF: 0.453

Gnomad NFE AF: 0.499

Gnomad OTH AF: 0.524

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

GnomAD4 genome AF: 0.573 AC: 80900 AN: 141074 Hom.: 24117 Cov.: 21 AF XY: 0.577 AC XY: 39280 AN XY: 68050

Gnomad4 AFR AF: 0.735

Gnomad4 AMR AF: 0.594

Gnomad4 ASJ AF: 0.308

Gnomad4 EAS AF: 0.479

Gnomad4 SAS AF: 0.628

Gnomad4 FIN AF: 0.584

Gnomad4 NFE AF: 0.499

Gnomad4 OTH AF: 0.520

Alfa AF: 0.539 Hom.: 4976

Bravo AF: 0.581

Asia WGS AF: 0.539 AC: 1858 AN: 3446

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	1.1
DANN	Benign	0.45

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

Other links and lift over

dbSNP: rs4673629; hg19: chr2-212586244;