2-212477413-T-C

Variant names:

Variant summary

Our verdict is . The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_005235.3(ERBB4):c.82+61036A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.158 in 152,076 control chromosomes in the GnomAD database, including 2,416 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 0.16 ( 2416 hom., cov: 32)

Consequence

ERBB4
NM_005235.3 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.104

Publications

2 publications found

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 Gene-Disease associations (from GenCC):

amyotrophic lateral sclerosis type 19
Inheritance: AD Classification: STRONG, MODERATE, LIMITED Submitted by: Ambry Genetics, Genomics England PanelApp, ClinGen, Labcorp Genetics (formerly Invitae)
intellectual disability
Inheritance: AD Classification: STRONG Submitted by: PanelApp Australia
amyotrophic lateral sclerosis
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ERBB4 links:

Genome browser will be placed here

new If you want to explore the variant's impact on the transcript NM_005235.3, check out the Mutation Effect Viewer. This is especially useful for frameshift variants or if you want to visualize the effect of exon loss / intron retention.

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.57).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.222 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005235.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
ERBB4	NM_005235.3	MANE Select	c.82+61036A>G	intron	N/A	NP_005226.1	Q15303-1
ERBB4	NM_001439005.1		c.82+61036A>G	intron	N/A	NP_001425934.1
ERBB4	NM_001042599.2		c.82+61036A>G	intron	N/A	NP_001036064.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
ERBB4	ENST00000342788.9	TSL:1 MANE Select	c.82+61036A>G	intron	N/A	ENSP00000342235.4	Q15303-1
ERBB4	ENST00000436443.5	TSL:1	c.82+61036A>G	intron	N/A	ENSP00000403204.1	Q15303-3
ERBB4	ENST00000484594.5	TSL:1	n.134+61036A>G	intron	N/A

Frequencies

GnomAD3 genomes

AF:

0.158

AC:

24075

AN:

151958

Hom.:

2416

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0589

Gnomad AMI

AF:

0.205

Gnomad AMR

AF:

0.127

Gnomad ASJ

AF:

0.238

Gnomad EAS

AF:

0.00596

Gnomad SAS

AF:

0.135

Gnomad FIN

AF:

0.218

Gnomad MID

AF:

0.130

Gnomad NFE

AF:

0.225

Gnomad OTH

AF:

0.167

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

GnomAD4 genome

AF:

0.158

AC:

24072

AN:

152076

Hom.:

2416

Cov.:

AF XY:

0.156

AC XY:

11584

AN XY:

74310

show subpopulations

African (AFR)

AF:

0.0587

AC:

2438

AN:

41512

American (AMR)

AF:

0.127

AC:

1933

AN:

15250

Ashkenazi Jewish (ASJ)

AF:

0.238

AC:

828

AN:

3472

East Asian (EAS)

AF:

0.00598

AC:

AN:

5188

South Asian (SAS)

AF:

0.136

AC:

654

AN:

4826

European-Finnish (FIN)

AF:

0.218

AC:

2305

AN:

10562

Middle Eastern (MID)

AF:

0.119

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.225

AC:

15313

AN:

67952

Other (OTH)

AF:

0.165

AC:

348

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

1023

2046

3068

4091

5114

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

260

520

780

1040

1300

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.109

Hom.:

242

Bravo

AF:

0.148

Asia WGS

AF:

0.0600

AC:

211

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.57

CADD

Benign

4.1

(source)

DANN

Benign

0.46

PhyloP100

-0.10

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over