rs13021324

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_005235.3(ERBB4):​c.2488-54420A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.23 in 151,972 control chromosomes in the GnomAD database, including 4,347 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 0.23 ( 4347 hom., cov: 30)

Consequence

ERBB4
NM_005235.3 intron

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.03
Variant links:
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.96).
BA1
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.321 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
ERBB4NM_005235.3 linkuse as main transcriptc.2488-54420A>G intron_variant ENST00000342788.9

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
ERBB4ENST00000342788.9 linkuse as main transcriptc.2488-54420A>G intron_variant 1 NM_005235.3 P4Q15303-1
ERBB4ENST00000436443.5 linkuse as main transcriptc.2488-54420A>G intron_variant 1 A1Q15303-3
ERBB4ENST00000260943.11 linkuse as main transcriptc.2458-54420A>G intron_variant 5 Q15303-4

Frequencies

GnomAD3 genomes
AF:
0.229
AC:
34824
AN:
151854
Hom.:
4333
Cov.:
30
show subpopulations
Gnomad AFR
AF:
0.325
Gnomad AMI
AF:
0.132
Gnomad AMR
AF:
0.232
Gnomad ASJ
AF:
0.158
Gnomad EAS
AF:
0.297
Gnomad SAS
AF:
0.152
Gnomad FIN
AF:
0.197
Gnomad MID
AF:
0.152
Gnomad NFE
AF:
0.182
Gnomad OTH
AF:
0.222
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome
AF:
0.230
AC:
34880
AN:
151972
Hom.:
4347
Cov.:
30
AF XY:
0.231
AC XY:
17145
AN XY:
74274
show subpopulations
Gnomad4 AFR
AF:
0.325
Gnomad4 AMR
AF:
0.232
Gnomad4 ASJ
AF:
0.158
Gnomad4 EAS
AF:
0.298
Gnomad4 SAS
AF:
0.150
Gnomad4 FIN
AF:
0.197
Gnomad4 NFE
AF:
0.182
Gnomad4 OTH
AF:
0.219
Alfa
AF:
0.172
Hom.:
1295
Bravo
AF:
0.236
Asia WGS
AF:
0.218
AC:
757
AN:
3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.96
CADD
Benign
0.22
DANN
Benign
0.71

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

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs13021324; hg19: chr2-212350245; API