rs7560730

chr2-212126143-C-T

Variant summary

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

The NM_005235.3(ERBB4):c.83-1240G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.835 in 152,144 control chromosomes in the GnomAD database, including 54,589 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 0.83 (54589 hom., cov: 32)
• Consequence: ERBB4 NM_005235.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.788

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=-1.03).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.952 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ERBB4	NM_005235.3	c.83-1240G>A		intron_variant		ENST00000342788.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ERBB4	ENST00000342788.9	c.83-1240G>A		intron_variant		1	NM_005235.3	P4

Frequencies

GnomAD3 genomes AF: 0.835 AC: 126880 AN: 152026 Hom.: 54538 Cov.: 32

Gnomad AFR AF: 0.960

Gnomad AMI AF: 0.748

Gnomad AMR AF: 0.718

Gnomad ASJ AF: 0.803

Gnomad EAS AF: 0.211

Gnomad SAS AF: 0.769

Gnomad FIN AF: 0.805

Gnomad MID AF: 0.801

Gnomad NFE AF: 0.843

Gnomad OTH AF: 0.850

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

GnomAD4 genome AF: 0.835 AC: 126987 AN: 152144 Hom.: 54589 Cov.: 32 AF XY: 0.825 AC XY: 61393 AN XY: 74376

Gnomad4 AFR AF: 0.960

Gnomad4 AMR AF: 0.717

Gnomad4 ASJ AF: 0.803

Gnomad4 EAS AF: 0.211

Gnomad4 SAS AF: 0.770

Gnomad4 FIN AF: 0.805

Gnomad4 NFE AF: 0.843

Gnomad4 OTH AF: 0.843

Alfa AF: 0.833 Hom.: 51186

Bravo AF: 0.828

Asia WGS AF: 0.510 AC: 1775 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
Cadd	Benign	0.18
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: rs7560730; hg19: chr2-212990868;