Variant 2-211380227-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_005235.3(ERBB4):c.*3388C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.6 in 231,818 control chromosomes in the GnomAD database, including 43,019 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.58 ( 26277 hom., cov: 31)

Exomes 𝑓: 0.64 ( 16742 hom. )

Consequence

ERBB4
NM_005235.3 3_prime_UTR

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.409

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]

ERBB4 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.92).

BP6

Variant 2-211380227-G-A is Benign according to our data. Variant chr2-211380227-G-A is described in ClinVar as [Benign]. Clinvar id is 1230173.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

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 link	c.*3388C>T		3_prime_UTR_variant	Exon 28 of 28	ENST00000342788.9	NP_005226.1	Q15303-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ERBB4	ENST00000342788 link	c.*3388C>T		3_prime_UTR_variant	Exon 28 of 28	1	NM_005235.3	ENSP00000342235.4		Q15303-1
ERBB4	ENST00000436443 link	c.*3388C>T		3_prime_UTR_variant	Exon 27 of 27	1		ENSP00000403204.1		Q15303-3

Frequencies

GnomAD3 genomes

AF:

0.578

AC:

87672

AN:

151656

Hom.:

26267

Cov.:

show subpopulations

Gnomad AFR

AF:

0.415

Gnomad AMI

AF:

0.557

Gnomad AMR

AF:

0.603

Gnomad ASJ

AF:

0.626

Gnomad EAS

AF:

0.752

Gnomad SAS

AF:

0.768

Gnomad FIN

AF:

0.625

Gnomad MID

AF:

0.602

Gnomad NFE

AF:

0.636

Gnomad OTH

AF:

0.560

GnomAD4 exome

AF:

0.642

AC:

51368

AN:

80044

Hom.:

16742

Cov.:

AF XY:

0.647

AC XY:

23814

AN XY:

36792

show subpopulations

Gnomad4 AFR exome

AF:

0.414

Gnomad4 AMR exome

AF:

0.606

Gnomad4 ASJ exome

AF:

0.631

Gnomad4 EAS exome

AF:

0.772

Gnomad4 SAS exome

AF:

0.741

Gnomad4 FIN exome

AF:

0.672

Gnomad4 NFE exome

AF:

0.636

Gnomad4 OTH exome

AF:

0.609

GnomAD4 genome

AF:

0.578

AC:

87710

AN:

151774

Hom.:

26277

Cov.:

AF XY:

0.582

AC XY:

43137

AN XY:

74174

show subpopulations

Gnomad4 AFR

AF:

0.414

Gnomad4 AMR

AF:

0.604

Gnomad4 ASJ

AF:

0.626

Gnomad4 EAS

AF:

0.753

Gnomad4 SAS

AF:

0.768

Gnomad4 FIN

AF:

0.625

Gnomad4 NFE

AF:

0.636

Gnomad4 OTH

AF:

0.559

Alfa

AF:

0.627

Hom.:

58632

Bravo

AF:

0.565

Asia WGS

AF:

0.688

AC:

2390

AN:

3476

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Feb 24, 2021

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is associated with the following publications: (PMID: 29125883) -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.92

CADD

Benign

0.44

DANN

Benign

0.37

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over