rs2271189

Positions:

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_001982.4(ERBB3):c.3348G>A(p.Arg1116Arg) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.373 in 1,613,462 control chromosomes in the GnomAD database, including 116,569 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.31 ( 8334 hom., cov: 30)

Exomes 𝑓: 0.38 ( 108235 hom. )

Consequence

ERBB3
NM_001982.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: -0.554

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:

ERBB3 (HGNC:):

ERBB3 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.53).

BP6

Variant 12-56101207-G-A is Benign according to our data. Variant chr12-56101207-G-A is described in ClinVar as [Benign]. Clinvar id is 1248586.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr12-56101207-G-A is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=-0.554 with no splicing effect.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.396 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ERBB3	NM_001982.4 linkuse as main transcript	c.3348G>A	p.Arg1116Arg	synonymous_variant	27/28	ENST00000267101.8	NP_001973.2	P21860-1
ERBB3	XM_047428500.1 linkuse as main transcript	c.3171G>A	p.Arg1057Arg	synonymous_variant	27/28		XP_047284456.1
ERBB3	XM_047428501.1 linkuse as main transcript	c.3171G>A	p.Arg1057Arg	synonymous_variant	27/28		XP_047284457.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ERBB3	ENST00000267101.8 linkuse as main transcript	c.3348G>A	p.Arg1116Arg	synonymous_variant	27/28	1	NM_001982.4	ENSP00000267101.4		P21860-1

Frequencies

GnomAD3 genomes

AF:

0.308

AC:

46725

AN:

151578

Hom.:

8330

Cov.:

show subpopulations

Gnomad AFR

AF:

0.124

Gnomad AMI

AF:

0.504

Gnomad AMR

AF:

0.340

Gnomad ASJ

AF:

0.381

Gnomad EAS

AF:

0.311

Gnomad SAS

AF:

0.249

Gnomad FIN

AF:

0.375

Gnomad MID

AF:

0.306

Gnomad NFE

AF:

0.400

Gnomad OTH

AF:

0.315

GnomAD3 exomes

AF:

0.347

AC:

87056

AN:

251170

Hom.:

15827

AF XY:

0.347

AC XY:

47112

AN XY:

135776

show subpopulations

Gnomad AFR exome

AF:

0.122

Gnomad AMR exome

AF:

0.356

Gnomad ASJ exome

AF:

0.361

Gnomad EAS exome

AF:

0.313

Gnomad SAS exome

AF:

0.256

Gnomad FIN exome

AF:

0.382

Gnomad NFE exome

AF:

0.398

Gnomad OTH exome

AF:

0.349

GnomAD4 exome

AF:

0.380

AC:

555279

AN:

1461766

Hom.:

108235

Cov.:

AF XY:

0.377

AC XY:

274491

AN XY:

727198

show subpopulations

Gnomad4 AFR exome

AF:

0.117

Gnomad4 AMR exome

AF:

0.356

Gnomad4 ASJ exome

AF:

0.369

Gnomad4 EAS exome

AF:

0.321

Gnomad4 SAS exome

AF:

0.259

Gnomad4 FIN exome

AF:

0.387

Gnomad4 NFE exome

AF:

0.402

Gnomad4 OTH exome

AF:

0.360

GnomAD4 genome

AF:

0.308

AC:

46746

AN:

151696

Hom.:

8334

Cov.:

AF XY:

0.306

AC XY:

22654

AN XY:

74134

show subpopulations

Gnomad4 AFR

AF:

0.124

Gnomad4 AMR

AF:

0.340

Gnomad4 ASJ

AF:

0.381

Gnomad4 EAS

AF:

0.312

Gnomad4 SAS

AF:

0.250

Gnomad4 FIN

AF:

0.375

Gnomad4 NFE

AF:

0.400

Gnomad4 OTH

AF:

0.314

Alfa

AF:

0.362

Hom.:

13530

Bravo

AF:

0.300

Asia WGS

AF:

0.274

AC:

954

AN:

3478

EpiCase

AF:

0.378

EpiControl

AF:

0.376

ClinVar

Significance: Benign

Submissions summary: Benign:4

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	Sep 05, 2019	- -

Lethal congenital contracture syndrome 2

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 30, 2021

- -

Visceral neuropathy, familial

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 30, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.53

CADD

Benign

1.8

DANN

Benign

0.86

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