rs11895168

Positions:

• chr2-211377467-A-C
• chr2-211377467-A-G
• chr2-211377467-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.*6148T>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.672 in 232,666 control chromosomes in the GnomAD database, including 52,834 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 0.68 (34940 hom., cov: 32)
  • Exomes 𝑓: 0.66 (17894 hom.)
• Consequence: ERBB4 NM_005235.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.152

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=-0.89).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.751 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ERBB4	NM_005235.3	c.*6148T>G		3_prime_UTR_variant	28/28	ENST00000342788.9	NP_005226.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ERBB4	ENST00000342788.9	c.*6148T>G		3_prime_UTR_variant	28/28	1	NM_005235.3	ENSP00000342235	P4
ERBB4	ENST00000436443.5	c.*6148T>G		3_prime_UTR_variant	27/27	1		ENSP00000403204	A1

Frequencies

GnomAD3 genomes AF: 0.676 AC: 102635 AN: 151896 Hom.: 34885 Cov.: 32

Gnomad AFR AF: 0.744

Gnomad AMI AF: 0.551

Gnomad AMR AF: 0.649

Gnomad ASJ AF: 0.607

Gnomad EAS AF: 0.747

Gnomad SAS AF: 0.772

Gnomad FIN AF: 0.626

Gnomad MID AF: 0.608

Gnomad NFE AF: 0.642

Gnomad OTH AF: 0.643

GnomAD4 exome AF: 0.664 AC: 53544 AN: 80652 Hom.: 17894 Cov.: 0 AF XY: 0.667 AC XY: 24753 AN XY: 37138

Gnomad4 AFR exome AF: 0.745

Gnomad4 AMR exome AF: 0.648

Gnomad4 ASJ exome AF: 0.613

Gnomad4 EAS exome AF: 0.767

Gnomad4 SAS exome AF: 0.741

Gnomad4 FIN exome AF: 0.654

Gnomad4 NFE exome AF: 0.641

Gnomad4 OTH exome AF: 0.650

GnomAD4 genome AF: 0.676 AC: 102755 AN: 152014 Hom.: 34940 Cov.: 32 AF XY: 0.678 AC XY: 50337 AN XY: 74284

Gnomad4 AFR AF: 0.745

Gnomad4 AMR AF: 0.649

Gnomad4 ASJ AF: 0.607

Gnomad4 EAS AF: 0.748

Gnomad4 SAS AF: 0.772

Gnomad4 FIN AF: 0.626

Gnomad4 NFE AF: 0.642

Gnomad4 OTH AF: 0.643

Alfa AF: 0.654 Hom.: 16722

Bravo AF: 0.678

Asia WGS AF: 0.713 AC: 2477 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.35
DANN	Benign	0.61

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: rs11895168; hg19: chr2-212242192; COSMIC: COSV61502032;