rs1047115

Variant names:

• chr3-186640577-A-C
• rs1047115
• NM_014375.3:c.117A>C

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_014375.3(FETUB):​c.117A>C​(p.Ser39Ser) 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
• Publications: 21 publications found

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

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
FETUB	NM_014375.3	c.117A>C	p.Ser39Ser	synonymous_variant	Exon 1 of 7	ENST00000265029.8	NP_055190.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FETUB	ENST00000265029.8	c.117A>C	p.Ser39Ser	synonymous_variant	Exon 1 of 7	1	NM_014375.3	ENSP00000265029.3

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

GnomAD2 exomes AF: 0.111 AC: 27826 AN: 250976 AF XY: 0.110

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 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

African (AFR) AF: 0.148 AC: 4951 AN: 33472

American (AMR) AF: 0.0567 AC: 2538 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.103 AC: 2692 AN: 26136

East Asian (EAS) AF: 0.130 AC: 5169 AN: 39700

South Asian (SAS) AF: 0.0739 AC: 6374 AN: 86258

European-Finnish (FIN) AF: 0.126 AC: 6749 AN: 53416

Middle Eastern (MID) AF: 0.119 AC: 688 AN: 5768

European-Non Finnish (NFE) AF: 0.130 AC: 144480 AN: 1111160

Other (OTH) AF: 0.121 AC: 7324 AN: 60380

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

African (AFR) AF: 0.148 AC: 6159 AN: 41514

American (AMR) AF: 0.0971 AC: 1485 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.111 AC: 386 AN: 3468

East Asian (EAS) AF: 0.112 AC: 582 AN: 5182

South Asian (SAS) AF: 0.0652 AC: 315 AN: 4830

European-Finnish (FIN) AF: 0.123 AC: 1304 AN: 10604

Middle Eastern (MID) AF: 0.105 AC: 31 AN: 294

European-Non Finnish (NFE) AF: 0.134 AC: 9090 AN: 67984

Other (OTH) AF: 0.113 AC: 239 AN: 2114

Alfa AF: 0.128 Hom.: 2275

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
PhyloP100		-3.4
PromoterAI		-0.31	Neutral
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

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