Variant 12-1028051-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP6BA1

The NM_178040.4(ERC1):c.148A>G(p.Ser50Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0339 in 1,614,182 control chromosomes in the GnomAD database, including 1,110 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.026 ( 81 hom., cov: 32)

Exomes 𝑓: 0.035 ( 1029 hom. )

Consequence

ERC1
NM_178040.4 missense

Scores

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: 1.96

Variant links:

Genes affected

ERC1 (HGNC:17072): (ELKS/RAB6-interacting/CAST family member 1) The protein encoded by this gene is a member of a family of RIM-binding proteins. RIMs are active zone proteins that regulate neurotransmitter release. This gene has been found fused to the receptor-type tyrosine kinase gene RET by gene rearrangement due to the translocation t(10;12)(q11;p13) in thyroid papillary carcinoma. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jul 2014]

ERC1 links:

ERC1 (HGNC:):

ERC1 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -13 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0029384196).

BP6

Variant 12-1028051-A-G is Benign according to our data. Variant chr12-1028051-A-G is described in ClinVar as [Benign]. Clinvar id is 3037380.Status of the report is no_assertion_criteria_provided, 0 stars.

BA1

GnomAdExome4 highest subpopulation (MID) allele frequency at 95% confidence interval = 0.0619 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ERC1	NM_178040.4 linkuse as main transcript	c.148A>G	p.Ser50Gly	missense_variant	2/19	ENST00000360905.9	NP_829884.1	Q8IUD2-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ERC1	ENST00000360905.9 linkuse as main transcript	c.148A>G	p.Ser50Gly	missense_variant	2/19	1	NM_178040.4	ENSP00000354158.3		Q8IUD2-1

Frequencies

GnomAD3 genomes

AF:

0.0262

AC:

3984

AN:

152188

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00671

Gnomad AMI

AF:

0.0428

Gnomad AMR

AF:

0.0343

Gnomad ASJ

AF:

0.0595

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.0130

Gnomad FIN

AF:

0.00687

Gnomad MID

AF:

0.0886

Gnomad NFE

AF:

0.0394

Gnomad OTH

AF:

0.0449

GnomAD3 exomes

AF:

0.0273

AC:

6874

AN:

251456

Hom.:

150

AF XY:

0.0275

AC XY:

3735

AN XY:

135898

show subpopulations

Gnomad AFR exome

AF:

0.00664

Gnomad AMR exome

AF:

0.0239

Gnomad ASJ exome

AF:

0.0634

Gnomad EAS exome

AF:

0.0000544

Gnomad SAS exome

AF:

0.0163

Gnomad FIN exome

AF:

0.00781

Gnomad NFE exome

AF:

0.0385

Gnomad OTH exome

AF:

0.0411

GnomAD4 exome

AF:

0.0347

AC:

50687

AN:

1461876

Hom.:

1029

Cov.:

AF XY:

0.0343

AC XY:

24971

AN XY:

727234

show subpopulations

Gnomad4 AFR exome

AF:

0.00568

Gnomad4 AMR exome

AF:

0.0250

Gnomad4 ASJ exome

AF:

0.0673

Gnomad4 EAS exome

AF:

0.0000504

Gnomad4 SAS exome

AF:

0.0170

Gnomad4 FIN exome

AF:

0.0101

Gnomad4 NFE exome

AF:

0.0388

Gnomad4 OTH exome

AF:

0.0350

GnomAD4 genome

AF:

0.0261

AC:

3977

AN:

152306

Hom.:

Cov.:

AF XY:

0.0244

AC XY:

1819

AN XY:

74476

show subpopulations

Gnomad4 AFR

AF:

0.00669

Gnomad4 AMR

AF:

0.0342

Gnomad4 ASJ

AF:

0.0595

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.0128

Gnomad4 FIN

AF:

0.00687

Gnomad4 NFE

AF:

0.0394

Gnomad4 OTH

AF:

0.0440

Alfa

AF:

0.0368

Hom.:

191

Bravo

AF:

0.0289

TwinsUK

AF:

0.0359

AC:

133

ALSPAC

AF:

0.0475

AC:

183

ESP6500AA

AF:

0.00840

AC:

ESP6500EA

AF:

0.0428

AC:

368

ExAC

AF:

0.0269

AC:

3261

Asia WGS

AF:

0.00808

AC:

AN:

3478

EpiCase

AF:

0.0437

EpiControl

AF:

0.0429

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

ERC1-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

May 28, 2019

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.056

BayesDel_addAF

Benign

-0.45

BayesDel_noAF

Benign

-0.39

CADD

Benign

DANN

Benign

0.93

DEOGEN2

Benign

0.11

.;.;.;T;.;.;.;T;T

Eigen

Benign

-0.74

Eigen_PC

Benign

-0.54

FATHMM_MKL

Uncertain

0.77

MetaRNN

Benign

0.0029

T;T;T;T;T;T;T;T;T

MetaSVM

Benign

-0.93

MutationAssessor

Benign

0.0

.;N;.;N;.;N;N;N;.

PrimateAI

Uncertain

0.51

PROVEAN

Benign

-0.37

.;N;N;N;.;.;N;.;N

REVEL

Benign

0.28

Sift

Benign

0.33

.;T;T;T;.;.;T;.;T

Sift4G

Benign

0.62

T;T;T;T;T;T;T;T;T

Polyphen

0.0

.;B;.;B;.;.;B;B;.

Vest4

0.086, 0.048, 0.079, 0.076, 0.11, 0.082, 0.089

MPC

0.30

ClinPred

0.0017

GERP RS

-0.43

Varity_R

0.042

gMVP

0.33

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