rs6147150

Positions:

• chr2-211380365-C-CTGAAAATAGGAT
• chr2-211380365-C-CTGAAAATAGG
• chr2-211380365-C-CTGAAAATAG

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BA1

The NM_005235.3(ERBB4):​c.*3249_*3250insATCCTATTTTCA variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.58 (26585 hom., cov: 0)
  • Exomes 𝑓: 0.64 (16855 hom.)
• Consequence: ERBB4 NM_005235.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.313

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 -8 ACMG points.

• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.747 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ERBB4	NM_005235.3	c.*3249_*3250insATCCTATTTTCA		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.*3249_*3250insATCCTATTTTCA		3_prime_UTR_variant	28/28	1	NM_005235.3	ENSP00000342235	P4
ERBB4	ENST00000436443.5	c.*3249_*3250insATCCTATTTTCA		3_prime_UTR_variant	27/27	1		ENSP00000403204	A1

Frequencies

GnomAD3 genomes AF: 0.584 AC: 88441 AN: 151312 Hom.: 26577 Cov.: 0

Gnomad AFR AF: 0.439

Gnomad AMI AF: 0.553

Gnomad AMR AF: 0.605

Gnomad ASJ AF: 0.625

Gnomad EAS AF: 0.747

Gnomad SAS AF: 0.769

Gnomad FIN AF: 0.626

Gnomad MID AF: 0.603

Gnomad NFE AF: 0.636

Gnomad OTH AF: 0.564

GnomAD4 exome AF: 0.643 AC: 51619 AN: 80236 Hom.: 16855 Cov.: 0 AF XY: 0.648 AC XY: 23918 AN XY: 36886

Gnomad4 AFR exome AF: 0.438

Gnomad4 AMR exome AF: 0.613

Gnomad4 ASJ exome AF: 0.631

Gnomad4 EAS exome AF: 0.771

Gnomad4 SAS exome AF: 0.741

Gnomad4 FIN exome AF: 0.672

Gnomad4 NFE exome AF: 0.636

Gnomad4 OTH exome AF: 0.610

GnomAD4 genome AF: 0.584 AC: 88479 AN: 151432 Hom.: 26585 Cov.: 0 AF XY: 0.587 AC XY: 43450 AN XY: 73970

Gnomad4 AFR AF: 0.438

Gnomad4 AMR AF: 0.605

Gnomad4 ASJ AF: 0.625

Gnomad4 EAS AF: 0.749

Gnomad4 SAS AF: 0.768

Gnomad4 FIN AF: 0.626

Gnomad4 NFE AF: 0.636

Gnomad4 OTH AF: 0.564

Alfa AF: 0.582 Hom.: 2773

Asia WGS AF: 0.688 AC: 2390 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs6147150; hg19: chr2-212245090;