rs1047115

Positions:

• chr3-186640577-A-C

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_014375.3(FETUB):​c.117A>C​(p.Ser39=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.124 in 1,613,202 control chromosomes in the GnomAD database, including 12,902 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.13 (1297 hom., cov: 32)
  • Exomes 𝑓: 0.12 (11605 hom.)
• Consequence: FETUB NM_014375.3 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.36

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]

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

ACMG classification

Verdict is Benign. Variant got -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BP7: Synonymous conserved (PhyloP=-3.36 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.145 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FETUB	NM_014375.3	c.117A>C	p.Ser39=	synonymous_variant	1/7	ENST00000265029.8	NP_055190.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FETUB	ENST00000265029.8	c.117A>C	p.Ser39=	synonymous_variant	1/7	1	NM_014375.3	ENSP00000265029	P1
HRG-AS1	ENST00000630178.2	n.239-60611T>G		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.129 AC: 19659 AN: 152070 Hom.: 1298 Cov.: 32

Gnomad AFR AF: 0.148

Gnomad AMI AF: 0.0811

Gnomad AMR AF: 0.0973

Gnomad ASJ AF: 0.111

Gnomad EAS AF: 0.113

Gnomad SAS AF: 0.0658

Gnomad FIN AF: 0.123

Gnomad MID AF: 0.108

Gnomad NFE AF: 0.134

Gnomad OTH AF: 0.114

GnomAD3 exomes AF: 0.111 AC: 27826 AN: 250976 Hom.: 1649 AF XY: 0.110 AC XY: 14910 AN XY: 135642

Gnomad AFR exome AF: 0.154

Gnomad AMR exome AF: 0.0531

Gnomad ASJ exome AF: 0.105

Gnomad EAS exome AF: 0.110

Gnomad SAS exome AF: 0.0740

Gnomad FIN exome AF: 0.123

Gnomad NFE exome AF: 0.130

Gnomad OTH exome AF: 0.117

GnomAD4 exome AF: 0.124 AC: 180965 AN: 1461014 Hom.: 11605 Cov.: 32 AF XY: 0.122 AC XY: 88714 AN XY: 726822

Gnomad4 AFR exome AF: 0.148

Gnomad4 AMR exome AF: 0.0567

Gnomad4 ASJ exome AF: 0.103

Gnomad4 EAS exome AF: 0.130

Gnomad4 SAS exome AF: 0.0739

Gnomad4 FIN exome AF: 0.126

Gnomad4 NFE exome AF: 0.130

Gnomad4 OTH exome AF: 0.121

GnomAD4 genome AF: 0.129 AC: 19665 AN: 152188 Hom.: 1297 Cov.: 32 AF XY: 0.126 AC XY: 9404 AN XY: 74408

Gnomad4 AFR AF: 0.148

Gnomad4 AMR AF: 0.0971

Gnomad4 ASJ AF: 0.111

Gnomad4 EAS AF: 0.112

Gnomad4 SAS AF: 0.0652

Gnomad4 FIN AF: 0.123

Gnomad4 NFE AF: 0.134

Gnomad4 OTH AF: 0.113

Alfa AF: 0.127 Hom.: 1654

Bravo AF: 0.128

Asia WGS AF: 0.107 AC: 372 AN: 3478

EpiCase AF: 0.126

EpiControl AF: 0.126

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	2.4
DANN	Benign	0.59

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.090		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

Other links and lift over

dbSNP: rs1047115; hg19: chr3-186358366; COSMIC: COSV54004980; COSMIC: COSV54004980;