rs6147150

Variant names:

• chr2-211380365-C-CTGAAAATAGGAT
• rs6147150
• NM_005235.3:c.*3249_*3250insATCCTATTTTCA

Your query was ambiguous. Multiple possible variants found:

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

Variant summary

Our verdict is Benign. The variant received -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. It is difficult to determine the true allele frequency of this variant because it is of type INS_BIG, and the frequency of such variant types in population databases may be underestimated and unreliable. 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
• Publications: 17 publications found

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]

ERBB4 Gene-Disease associations (from GenCC):

• amyotrophic lateral sclerosis type 19

  Inheritance: AD Classification: STRONG, MODERATE, LIMITED Submitted by: ClinGen, Ambry Genetics, Labcorp Genetics (formerly Invitae), Genomics England PanelApp
• amyotrophic lateral sclerosis

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
ERBB4	NM_005235.3	c.*3249_*3250insATCCTATTTTCA		3_prime_UTR_variant	Exon 28 of 28	ENST00000342788.9	NP_005226.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ERBB4	ENST00000342788.9	c.*3249_*3250insATCCTATTTTCA		3_prime_UTR_variant	Exon 28 of 28	1	NM_005235.3	ENSP00000342235.4
ERBB4	ENST00000436443.5	c.*3249_*3250insATCCTATTTTCA		3_prime_UTR_variant	Exon 27 of 27	1		ENSP00000403204.1

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

African (AFR) AF: 0.438 AC: 1690 AN: 3856

American (AMR) AF: 0.613 AC: 1524 AN: 2488

Ashkenazi Jewish (ASJ) AF: 0.631 AC: 3192 AN: 5062

East Asian (EAS) AF: 0.771 AC: 8724 AN: 11308

South Asian (SAS) AF: 0.741 AC: 514 AN: 694

European-Finnish (FIN) AF: 0.672 AC: 39 AN: 58

Middle Eastern (MID) AF: 0.649 AC: 314 AN: 484

European-Non Finnish (NFE) AF: 0.636 AC: 31522 AN: 49570

Other (OTH) AF: 0.610 AC: 4100 AN: 6716

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

African (AFR) AF: 0.438 AC: 18099 AN: 41296

American (AMR) AF: 0.605 AC: 9184 AN: 15174

Ashkenazi Jewish (ASJ) AF: 0.625 AC: 2164 AN: 3464

East Asian (EAS) AF: 0.749 AC: 3827 AN: 5112

South Asian (SAS) AF: 0.768 AC: 3675 AN: 4784

European-Finnish (FIN) AF: 0.626 AC: 6604 AN: 10554

Middle Eastern (MID) AF: 0.606 AC: 177 AN: 292

European-Non Finnish (NFE) AF: 0.636 AC: 43059 AN: 67740

Other (OTH) AF: 0.564 AC: 1189 AN: 2110

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

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.31
Mutation Taster		=100/0	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs6147150; hg19: chr2-212245090; COSMIC: COSV61472393;