Variant 3-186644854-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_StrongBP6_ModerateBP7BS2

The NM_014375.3(FETUB):c.528G>A(p.Ala176Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00502 in 1,613,762 control chromosomes in the GnomAD database, including 38 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0035 ( 2 hom., cov: 32)

Exomes 𝑓: 0.0052 ( 36 hom. )

Consequence

FETUB
NM_014375.3 synonymous

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.0730

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 -11 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.52).

BP6

Variant 3-186644854-G-A is Benign according to our data. Variant chr3-186644854-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 2654335.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=0.073 with no splicing effect.

BS2

High Homozygotes in GnomAd4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FETUB	NM_014375.3 link	c.528G>A	p.Ala176Ala	synonymous_variant	Exon 4 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.528G>A	p.Ala176Ala	synonymous_variant	Exon 4 of 7	1	NM_014375.3	ENSP00000265029.3		Q9UGM5-1

Frequencies

GnomAD3 genomes

AF:

0.00349

AC:

530

AN:

151950

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00126

Gnomad AMI

AF:

0.00110

Gnomad AMR

AF:

0.00203

Gnomad ASJ

AF:

0.00864

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00291

Gnomad FIN

AF:

0.00104

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00560

Gnomad OTH

AF:

0.00478

GnomAD3 exomes

AF:

0.00397

AC:

996

AN:

251068

Hom.:

AF XY:

0.00429

AC XY:

582

AN XY:

135694

show subpopulations

Gnomad AFR exome

AF:

0.000677

Gnomad AMR exome

AF:

0.00252

Gnomad ASJ exome

AF:

0.00785

Gnomad EAS exome

AF:

0.0000544

Gnomad SAS exome

AF:

0.00353

Gnomad FIN exome

AF:

0.00140

Gnomad NFE exome

AF:

0.00577

Gnomad OTH exome

AF:

0.00408

GnomAD4 exome

AF:

0.00518

AC:

7565

AN:

1461694

Hom.:

Cov.:

AF XY:

0.00521

AC XY:

3791

AN XY:

727166

show subpopulations

Gnomad4 AFR exome

AF:

0.000806

Gnomad4 AMR exome

AF:

0.00291

Gnomad4 ASJ exome

AF:

0.00853

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.00347

Gnomad4 FIN exome

AF:

0.00137

Gnomad4 NFE exome

AF:

0.00584

Gnomad4 OTH exome

AF:

0.00479

GnomAD4 genome

AF:

0.00349

AC:

530

AN:

152068

Hom.:

Cov.:

AF XY:

0.00322

AC XY:

239

AN XY:

74316

show subpopulations

Gnomad4 AFR

AF:

0.00125

Gnomad4 AMR

AF:

0.00203

Gnomad4 ASJ

AF:

0.00864

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00291

Gnomad4 FIN

AF:

0.00104

Gnomad4 NFE

AF:

0.00560

Gnomad4 OTH

AF:

0.00473

Alfa

AF:

0.00556

Hom.:

Bravo

AF:

0.00337

Asia WGS

AF:

0.00144

AC:

AN:

3478

EpiCase

AF:

0.00638

EpiControl

AF:

0.00771

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Mar 01, 2023

CeGaT Center for Human Genetics Tuebingen

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

FETUB: BP4, BP7, BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.52

CADD

Benign

DANN

Benign

0.74

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