rs7564590

Positions:

• chr2-212523176-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.82+15273G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.411 in 151,634 control chromosomes in the GnomAD database, including 14,790 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 0.41 (14790 hom., cov: 32)
• Consequence: ERBB4 NM_005235.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.154

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=-0.95).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.66 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ERBB4	NM_005235.3	c.82+15273G>A		intron_variant		ENST00000342788.9	NP_005226.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ERBB4	ENST00000342788.9	c.82+15273G>A		intron_variant		1	NM_005235.3	ENSP00000342235	P4
ERBB4	ENST00000436443.5	c.82+15273G>A		intron_variant		1		ENSP00000403204	A1
ERBB4	ENST00000484594.5	n.134+15273G>A		intron_variant, non_coding_transcript_variant		1
ERBB4	ENST00000260943.11	c.82+15273G>A		intron_variant		5		ENSP00000260943

Frequencies

GnomAD3 genomes AF: 0.410 AC: 62151 AN: 151516 Hom.: 14739 Cov.: 32

Gnomad AFR AF: 0.666

Gnomad AMI AF: 0.280

Gnomad AMR AF: 0.326

Gnomad ASJ AF: 0.275

Gnomad EAS AF: 0.107

Gnomad SAS AF: 0.341

Gnomad FIN AF: 0.340

Gnomad MID AF: 0.272

Gnomad NFE AF: 0.323

Gnomad OTH AF: 0.365

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

GnomAD4 genome AF: 0.411 AC: 62273 AN: 151634 Hom.: 14790 Cov.: 32 AF XY: 0.407 AC XY: 30152 AN XY: 74108

Gnomad4 AFR AF: 0.667

Gnomad4 AMR AF: 0.326

Gnomad4 ASJ AF: 0.275

Gnomad4 EAS AF: 0.107

Gnomad4 SAS AF: 0.343

Gnomad4 FIN AF: 0.340

Gnomad4 NFE AF: 0.323

Gnomad4 OTH AF: 0.361

Alfa AF: 0.388 Hom.: 2411

Bravo AF: 0.421

Asia WGS AF: 0.256 AC: 890 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	1.4
DANN	Benign	0.25

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: rs7564590; hg19: chr2-213387900;