Variant 12-56080108-A-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2

The NM_001005915.1(ERBB3):c.-193A>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00974 in 557,124 control chromosomes in the GnomAD database, including 25 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.010 ( 16 hom., cov: 33)

Exomes 𝑓: 0.0096 ( 9 hom. )

Consequence

ERBB3
NM_001005915.1 5_prime_UTR

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.848

Variant links:

Genes affected

ERBB3 (HGNC:3431): (erb-b2 receptor tyrosine kinase 3) This gene encodes a member of the epidermal growth factor receptor (EGFR) family of receptor tyrosine kinases. This membrane-bound protein has a neuregulin binding domain but not an active kinase domain. It therefore can bind this ligand but not convey the signal into the cell through protein phosphorylation. However, it does form heterodimers with other EGF receptor family members which do have kinase activity. Heterodimerization leads to the activation of pathways which lead to cell proliferation or differentiation. Amplification of this gene and/or overexpression of its protein have been reported in numerous cancers, including prostate, bladder, and breast tumors. Alternate transcriptional splice variants encoding different isoforms have been characterized. One isoform lacks the intermembrane region and is secreted outside the cell. This form acts to modulate the activity of the membrane-bound form. Additional splice variants have also been reported, but they have not been thoroughly characterized. [provided by RefSeq, Jul 2008]

ERBB3 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.81).

BP6

Variant 12-56080108-A-T is Benign according to our data. Variant chr12-56080108-A-T is described in ClinVar as [Likely_benign]. Clinvar id is 1316548.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0101 (1522/150564) while in subpopulation NFE AF= 0.0136 (922/67556). AF 95% confidence interval is 0.0129. There are 16 homozygotes in gnomad4. There are 743 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 16 AD,AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ERBB3	NM_001005915.1 linkuse as main transcript	c.-193A>T		5_prime_UTR_variant	1/3		NP_001005915.1

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	Protein
ERBB3	ENST00000549061.5 linkuse as main transcript	c.-134+174A>T	intron_variant	4	ENSP00000449138
ERBB3	ENST00000549282.5 linkuse as main transcript	c.-104-89A>T	intron_variant	4	ENSP00000448636
ERBB3	ENST00000643266.1 linkuse as main transcript	c.-96+3225A>T	intron_variant		ENSP00000495453

Frequencies

GnomAD3 genomes

AF:

0.0101

AC:

1514

AN:

150456

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00648

Gnomad AMI

AF:

0.0265

Gnomad AMR

AF:

0.000990

Gnomad ASJ

AF:

0.00406

Gnomad EAS

AF:

0.000195

Gnomad SAS

AF:

0.00336

Gnomad FIN

AF:

0.0240

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0136

Gnomad OTH

AF:

0.00435

GnomAD4 exome

AF:

0.00960

AC:

3904

AN:

406560

Hom.:

Cov.:

AF XY:

0.00936

AC XY:

2021

AN XY:

215936

show subpopulations

Gnomad4 AFR exome

AF:

0.00737

Gnomad4 AMR exome

AF:

0.000706

Gnomad4 ASJ exome

AF:

0.00269

Gnomad4 EAS exome

AF:

0.000111

Gnomad4 SAS exome

AF:

0.00450

Gnomad4 FIN exome

AF:

0.0225

Gnomad4 NFE exome

AF:

0.0117

Gnomad4 OTH exome

AF:

0.00847

GnomAD4 genome

AF:

0.0101

AC:

1522

AN:

150564

Hom.:

Cov.:

AF XY:

0.0101

AC XY:

743

AN XY:

73524

show subpopulations

Gnomad4 AFR

AF:

0.00666

Gnomad4 AMR

AF:

0.000989

Gnomad4 ASJ

AF:

0.00406

Gnomad4 EAS

AF:

0.000196

Gnomad4 SAS

AF:

0.00336

Gnomad4 FIN

AF:

0.0240

Gnomad4 NFE

AF:

0.0136

Gnomad4 OTH

AF:

0.00431

Alfa

AF:

0.0200

Hom.:

Bravo

AF:

0.00716

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

Nov 11, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.81

CADD

Benign

1.1

DANN

Benign

0.73

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