Variant 3-186640508-C-G 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_014375.3(FETUB):c.48C>G(p.Cys16Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00575 in 1,614,146 control chromosomes in the GnomAD database, including 454 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.030 ( 211 hom., cov: 32)

Exomes 𝑓: 0.0032 ( 243 hom. )

Consequence

FETUB
NM_014375.3 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: -3.70

Variant links:

Genes affected

FETUB (HGNC:3658): (fetuin B) The protein encoded by this gene is a member of the fetuin family, part of the cystatin superfamily of cysteine protease inhibitors. Fetuins have been implicated in several diverse functions, including osteogenesis and bone resorption, regulation of the insulin and hepatocyte growth factor receptors, and response to systemic inflammation. This protein may be secreted by cells. [provided by RefSeq, Jul 2008]

FETUB links:

HRG-AS1 (HGNC:55915): (HRG and FETUB antisense RNA 1)

HRG-AS1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.00187096).

BP6

Variant 3-186640508-C-G is Benign according to our data. Variant chr3-186640508-C-G is described in ClinVar as [Benign]. Clinvar id is 775931.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0999 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FETUB	NM_014375.3 link	c.48C>G	p.Cys16Trp	missense_variant	Exon 1 of 7	ENST00000265029.8	NP_055190.2	Q9UGM5-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FETUB	ENST00000265029.8 link	c.48C>G	p.Cys16Trp	missense_variant	Exon 1 of 7	1	NM_014375.3	ENSP00000265029.3		Q9UGM5-1

Frequencies

GnomAD3 genomes

AF:

0.0298

AC:

4529

AN:

152160

Hom.:

210

Cov.:

show subpopulations

Gnomad AFR

AF:

0.102

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0125

Gnomad ASJ

AF:

0.00202

Gnomad EAS

AF:

0.000192

Gnomad SAS

AF:

0.000622

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.000485

Gnomad OTH

AF:

0.0263

GnomAD3 exomes

AF:

0.00779

AC:

1955

AN:

251090

Hom.:

102

AF XY:

0.00557

AC XY:

756

AN XY:

135684

show subpopulations

Gnomad AFR exome

AF:

0.105

Gnomad AMR exome

AF:

0.00483

Gnomad ASJ exome

AF:

0.00209

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000261

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000282

Gnomad OTH exome

AF:

0.00343

GnomAD4 exome

AF:

0.00324

AC:

4738

AN:

1461868

Hom.:

243

Cov.:

AF XY:

0.00276

AC XY:

2009

AN XY:

727242

show subpopulations

Gnomad4 AFR exome

AF:

0.110

Gnomad4 AMR exome

AF:

0.00566

Gnomad4 ASJ exome

AF:

0.00241

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.000220

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000236

Gnomad4 OTH exome

AF:

0.00687

GnomAD4 genome

AF:

0.0299

AC:

4548

AN:

152278

Hom.:

211

Cov.:

AF XY:

0.0290

AC XY:

2161

AN XY:

74464

show subpopulations

Gnomad4 AFR

AF:

0.102

Gnomad4 AMR

AF:

0.0125

Gnomad4 ASJ

AF:

0.00202

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.000622

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000485

Gnomad4 OTH

AF:

0.0260

Alfa

AF:

0.00193

Hom.:

Bravo

AF:

0.0340

TwinsUK

AF:

0.00

AC:

ALSPAC

AF:

0.000519

AC:

ESP6500AA

AF:

0.0976

AC:

430

ESP6500EA

AF:

0.000581

AC:

ExAC

AF:

0.00938

AC:

1139

Asia WGS

AF:

0.00346

AC:

AN:

3478

EpiCase

AF:

0.000382

EpiControl

AF:

0.000356

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Dec 31, 2019

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.15

BayesDel_addAF

Benign

-0.52

BayesDel_noAF

Benign

-0.43

CADD

Benign

0.0050

DANN

Benign

0.63

DEOGEN2

Benign

0.11

T;.;T;.

Eigen

Benign

-1.2

Eigen_PC

Benign

-1.5

FATHMM_MKL

Benign

0.068

LIST_S2

Benign

0.57

.;T;T;T

MetaRNN

Benign

0.0019

T;T;T;T

MetaSVM

Benign

-0.62

MutationAssessor

Benign

1.9

L;.;L;L

PrimateAI

Benign

0.45

PROVEAN

Pathogenic

-6.9

D;D;D;D

REVEL

Benign

0.22

Sift

Uncertain

0.0050

D;D;D;D

Sift4G

Benign

0.15

T;T;T;T

Polyphen

1.0

D;D;D;.

Vest4

0.49

MVP

0.13

MPC

0.033

ClinPred

0.11

GERP RS

-10

Varity_R

0.29

gMVP

0.66

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.13

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