Variant 12-56083705-G-T 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_001982.4(ERBB3):c.83-46G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00421 in 1,611,200 control chromosomes in the GnomAD database, including 226 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.022 ( 131 hom., cov: 32)

Exomes 𝑓: 0.0024 ( 95 hom. )

Consequence

ERBB3
NM_001982.4 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.332

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 -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.82).

BP6

Variant 12-56083705-G-T is Benign according to our data. Variant chr12-56083705-G-T is described in ClinVar as [Benign]. Clinvar id is 1182433.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0725 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	MANE	Protein
ERBB3	NM_001982.4 linkuse as main transcript	c.83-46G>T	intron_variant	ENST00000267101.8	NP_001973.2
ERBB3	NM_001005915.1 linkuse as main transcript	c.83-46G>T	intron_variant		NP_001005915.1
ERBB3	XM_047428500.1 linkuse as main transcript	c.-95-46G>T	intron_variant		XP_047284456.1
ERBB3	XM_047428501.1 linkuse as main transcript	c.-95-46G>T	intron_variant		XP_047284457.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ERBB3	ENST00000267101.8 linkuse as main transcript	c.83-46G>T		intron_variant		1	NM_001982.4	ENSP00000267101	P1	P21860-1

Frequencies

GnomAD3 genomes

AF:

0.0218

AC:

3310

AN:

152112

Hom.:

129

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0746

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00805

Gnomad ASJ

AF:

0.000576

Gnomad EAS

AF:

0.00790

Gnomad SAS

AF:

0.000621

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.000206

Gnomad OTH

AF:

0.0192

GnomAD3 exomes

AF:

0.00583

AC:

1465

AN:

251326

Hom.:

AF XY:

0.00452

AC XY:

614

AN XY:

135838

show subpopulations

Gnomad AFR exome

AF:

0.0743

Gnomad AMR exome

AF:

0.00298

Gnomad ASJ exome

AF:

0.000298

Gnomad EAS exome

AF:

0.00495

Gnomad SAS exome

AF:

0.000719

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000123

Gnomad OTH exome

AF:

0.00391

GnomAD4 exome

AF:

0.00237

AC:

3458

AN:

1458970

Hom.:

Cov.:

AF XY:

0.00217

AC XY:

1578

AN XY:

726000

show subpopulations

Gnomad4 AFR exome

AF:

0.0751

Gnomad4 AMR exome

AF:

0.00407

Gnomad4 ASJ exome

AF:

0.000383

Gnomad4 EAS exome

AF:

0.00524

Gnomad4 SAS exome

AF:

0.000743

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000730

Gnomad4 OTH exome

AF:

0.00643

GnomAD4 genome

AF:

0.0219

AC:

3328

AN:

152230

Hom.:

131

Cov.:

AF XY:

0.0213

AC XY:

1586

AN XY:

74424

show subpopulations

Gnomad4 AFR

AF:

0.0747

Gnomad4 AMR

AF:

0.00804

Gnomad4 ASJ

AF:

0.000576

Gnomad4 EAS

AF:

0.00773

Gnomad4 SAS

AF:

0.000415

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000206

Gnomad4 OTH

AF:

0.0223

Alfa

AF:

0.00505

Hom.:

Bravo

AF:

0.0235

Asia WGS

AF:

0.0320

AC:

112

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Nov 15, 2019	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.82

CADD

Benign

4.4

DANN

Benign

0.70

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.040

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