chr2-212300522-C-A

Position:

• chr2-212300522-C-A

Variant summary

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

The NM_005235.3(ERBB4):​c.83-175619G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.804 in 151,242 control chromosomes in the GnomAD database, including 50,423 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 0.80 (50423 hom., cov: 31)
• Consequence: ERBB4 NM_005235.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.355

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=-0.91).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.895 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ERBB4	NM_005235.3	c.83-175619G>T		intron_variant		ENST00000342788.9	NP_005226.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ERBB4	ENST00000342788.9	c.83-175619G>T		intron_variant		1	NM_005235.3	ENSP00000342235	P4

Frequencies

GnomAD3 genomes AF: 0.804 AC: 121559 AN: 151122 Hom.: 50414 Cov.: 31

Gnomad AFR AF: 0.582

Gnomad AMI AF: 0.976

Gnomad AMR AF: 0.860

Gnomad ASJ AF: 0.871

Gnomad EAS AF: 0.877

Gnomad SAS AF: 0.798

Gnomad FIN AF: 0.896

Gnomad MID AF: 0.880

Gnomad NFE AF: 0.901

Gnomad OTH AF: 0.823

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

GnomAD4 genome AF: 0.804 AC: 121616 AN: 151242 Hom.: 50423 Cov.: 31 AF XY: 0.804 AC XY: 59429 AN XY: 73912

Gnomad4 AFR AF: 0.582

Gnomad4 AMR AF: 0.859

Gnomad4 ASJ AF: 0.871

Gnomad4 EAS AF: 0.877

Gnomad4 SAS AF: 0.798

Gnomad4 FIN AF: 0.896

Gnomad4 NFE AF: 0.901

Gnomad4 OTH AF: 0.824

Alfa AF: 0.858 Hom.: 15861

Bravo AF: 0.793

Asia WGS AF: 0.814 AC: 2828 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	2.0
DANN	Benign	0.42

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: rs13392330; hg19: chr2-213165247;