2-211751995-G-C

Position:

• chr2-211751995-G-C

Variant summary

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

The ENST00000342788.9(ERBB4):​c.557-1291C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.34 in 151,938 control chromosomes in the GnomAD database, including 8,886 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 0.34 (8886 hom., cov: 32)
• Consequence: ERBB4 ENST00000342788.9 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.26

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=-0.47).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.427 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ERBB4	NM_005235.3	c.557-1291C>G		intron_variant		ENST00000342788.9	NP_005226.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ERBB4	ENST00000342788.9	c.557-1291C>G		intron_variant		1	NM_005235.3	ENSP00000342235	P4

Frequencies

GnomAD3 genomes AF: 0.340 AC: 51588 AN: 151820 Hom.: 8883 Cov.: 32

Gnomad AFR AF: 0.351

Gnomad AMI AF: 0.250

Gnomad AMR AF: 0.331

Gnomad ASJ AF: 0.295

Gnomad EAS AF: 0.316

Gnomad SAS AF: 0.443

Gnomad FIN AF: 0.354

Gnomad MID AF: 0.389

Gnomad NFE AF: 0.330

Gnomad OTH AF: 0.344

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

GnomAD4 genome AF: 0.340 AC: 51617 AN: 151938 Hom.: 8886 Cov.: 32 AF XY: 0.342 AC XY: 25427 AN XY: 74242

Gnomad4 AFR AF: 0.351

Gnomad4 AMR AF: 0.331

Gnomad4 ASJ AF: 0.295

Gnomad4 EAS AF: 0.317

Gnomad4 SAS AF: 0.443

Gnomad4 FIN AF: 0.354

Gnomad4 NFE AF: 0.330

Gnomad4 OTH AF: 0.340

Alfa AF: 0.318 Hom.: 938

Bravo AF: 0.333

Asia WGS AF: 0.332 AC: 1157 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.47
CADD	Benign	8.0
DANN	Benign	0.53

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: rs6749096; hg19: chr2-212616720;