2-212323745-C-T

Variant names:

• chr2-212323745-C-T
• rs905883
• NM_005235.3:c.83-198842G>A

Variant summary

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

The NM_005235.3(ERBB4):​c.83-198842G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.771 in 150,082 control chromosomes in the GnomAD database, including 47,188 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 0.77 (47188 hom., cov: 31)
• Consequence: ERBB4 NM_005235.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.439

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=-0.9).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.886 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ERBB4	NM_005235.3	c.83-198842G>A		intron_variant	Intron 1 of 27	ENST00000342788.9	NP_005226.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ERBB4	ENST00000342788.9	c.83-198842G>A		intron_variant	Intron 1 of 27	1	NM_005235.3	ENSP00000342235.4

Frequencies

GnomAD3 genomes AF: 0.771 AC: 115605 AN: 149962 Hom.: 47186 Cov.: 31

Gnomad AFR AF: 0.525

Gnomad AMI AF: 0.976

Gnomad AMR AF: 0.793

Gnomad ASJ AF: 0.859

Gnomad EAS AF: 0.767

Gnomad SAS AF: 0.777

Gnomad FIN AF: 0.875

Gnomad MID AF: 0.864

Gnomad NFE AF: 0.892

Gnomad OTH AF: 0.796

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

GnomAD4 genome AF: 0.771 AC: 115649 AN: 150082 Hom.: 47188 Cov.: 31 AF XY: 0.770 AC XY: 56472 AN XY: 73294

Gnomad4 AFR AF: 0.524

Gnomad4 AMR AF: 0.792

Gnomad4 ASJ AF: 0.859

Gnomad4 EAS AF: 0.766

Gnomad4 SAS AF: 0.777

Gnomad4 FIN AF: 0.875

Gnomad4 NFE AF: 0.892

Gnomad4 OTH AF: 0.798

Alfa AF: 0.851 Hom.: 19478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	1.4
DANN	Benign	0.66

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: rs905883; hg19: chr2-213188470;