rs1836721

chr2-211387469-A-T

Variant summary

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

The NM_005235.3(ERBB4):c.3184-319T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0811 in 152,258 control chromosomes in the GnomAD database, including 728 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 0.081 (728 hom., cov: 32)
• Consequence: ERBB4 NM_005235.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.641

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=-0.8).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.119 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ERBB4	NM_005235.3	c.3184-319T>A		intron_variant		ENST00000342788.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ERBB4	ENST00000342788.9	c.3184-319T>A		intron_variant		1	NM_005235.3	P4
ERBB4	ENST00000436443.5	c.3136-319T>A		intron_variant		1		A1
ERBB4	ENST00000260943.11	c.3106-319T>A		intron_variant		5

Frequencies

GnomAD3 genomes AF: 0.0812 AC: 12356 AN: 152140 Hom.: 729 Cov.: 32

Gnomad AFR AF: 0.0200

Gnomad AMI AF: 0.168

Gnomad AMR AF: 0.0907

Gnomad ASJ AF: 0.158

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.0253

Gnomad FIN AF: 0.0758

Gnomad MID AF: 0.180

Gnomad NFE AF: 0.121

Gnomad OTH AF: 0.0946

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

GnomAD4 genome AF: 0.0811 AC: 12345 AN: 152258 Hom.: 728 Cov.: 32 AF XY: 0.0778 AC XY: 5793 AN XY: 74434

Gnomad4 AFR AF: 0.0199

Gnomad4 AMR AF: 0.0905

Gnomad4 ASJ AF: 0.158

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.0255

Gnomad4 FIN AF: 0.0758

Gnomad4 NFE AF: 0.121

Gnomad4 OTH AF: 0.0937

Alfa AF: 0.0957 Hom.: 118

Bravo AF: 0.0820

Asia WGS AF: 0.0140 AC: 51 AN: 3468

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
Cadd	Benign	11
Dann	Benign	0.72

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: rs1836721; hg19: chr2-212252194;