rs7588550

Variant names:

• chr2-212304043-G-A
• rs7588550
• NM_005235.3:c.83-179140C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_005235.3(ERBB4):​c.83-179140C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.958 in 151,582 control chromosomes in the GnomAD database, including 69,609 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 0.96 (69609 hom., cov: 33)
• Consequence: ERBB4 NM_005235.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.55
• Publications: 29 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.984 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ERBB4	NM_005235.3	c.83-179140C>T		intron_variant	Intron 1 of 27	ENST00000342788.9	NP_005226.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ERBB4	ENST00000342788.9	c.83-179140C>T		intron_variant	Intron 1 of 27	1	NM_005235.3	ENSP00000342235.4

Frequencies

GnomAD3 genomes AF: 0.958 AC: 145085 AN: 151464 Hom.: 69560 Cov.: 33

Gnomad AFR AF: 0.992

Gnomad AMI AF: 0.990

Gnomad AMR AF: 0.935

Gnomad ASJ AF: 0.939

Gnomad EAS AF: 0.885

Gnomad SAS AF: 0.922

Gnomad FIN AF: 0.922

Gnomad MID AF: 0.975

Gnomad NFE AF: 0.956

Gnomad OTH AF: 0.959

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

GnomAD4 genome AF: 0.958 AC: 145190 AN: 151582 Hom.: 69609 Cov.: 33 AF XY: 0.954 AC XY: 70644 AN XY: 74076

African (AFR) AF: 0.992 AC: 41200 AN: 41512

American (AMR) AF: 0.935 AC: 14182 AN: 15174

Ashkenazi Jewish (ASJ) AF: 0.939 AC: 3242 AN: 3452

East Asian (EAS) AF: 0.885 AC: 4528 AN: 5116

South Asian (SAS) AF: 0.922 AC: 4448 AN: 4824

European-Finnish (FIN) AF: 0.922 AC: 9781 AN: 10612

Middle Eastern (MID) AF: 0.983 AC: 289 AN: 294

European-Non Finnish (NFE) AF: 0.956 AC: 64605 AN: 67586

Other (OTH) AF: 0.958 AC: 2012 AN: 2100

Alfa AF: 0.961 Hom.: 37580

Bravo AF: 0.959

Asia WGS AF: 0.903 AC: 3138 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.021
DANN	Benign	0.57
PhyloP100		-3.6
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs7588550; hg19: chr2-213168768;