rs116454156

Variant names:

• chr10-93587284-G-A
• rs116454156
• NM_001195755.2:c.761G>A

Your query was ambiguous. Multiple possible variants found:

• chr10-93587284-G-A
• chr10-93587284-G-C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_001195755.2(FFAR4):​c.761G>A​(p.Arg254His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0174 in 1,614,070 control chromosomes in the GnomAD database, including 393 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.014 (39 hom., cov: 31)
  • Exomes 𝑓: 0.018 (354 hom.)
• Consequence: FFAR4 NM_001195755.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1 O:1
• Conservation: PhyloP100: 1.75
• Publications: 62 publications found

Genes affected

FFAR4 (HGNC:19061): (free fatty acid receptor 4) This gene encodes a G protein-coupled receptor (GPR) which belongs to the rhodopsin family of GPRs. The encoded protein functions as a receptor for free fatty acids, including omega-3, and participates in suppressing anti-inflammatory responses and insulin sensitizing. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Feb 2012]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.002275765).
• BS1: Variant frequency is greater than expected in population sas. GnomAd4 allele frequency = 0.0143 (2180/152256) while in subpopulation SAS AF = 0.0399 (192/4810). AF 95% confidence interval is 0.0353. There are 39 homozygotes in GnomAd4. There are 1061 alleles in the male GnomAd4 subpopulation. Median coverage is 31. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 39 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001195755.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FFAR4	NM_001195755.2	MANE Select	c.761G>A	p.Arg254His	missense	Exon 3 of 3	NP_001182684.1	Q5NUL3-2
	FFAR4	NM_181745.4		c.809G>A	p.Arg270His	missense	Exon 4 of 4	NP_859529.2	Q5NUL3-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FFAR4	ENST00000371481.9	TSL:1 MANE Select	c.761G>A	p.Arg254His	missense	Exon 3 of 3	ENSP00000360536.5	Q5NUL3-2
	FFAR4	ENST00000371483.8	TSL:1	c.809G>A	p.Arg270His	missense	Exon 4 of 4	ENSP00000360538.4	Q5NUL3-1
	FFAR4	ENST00000944863.1		c.632G>A	p.Arg211His	missense	Exon 2 of 2	ENSP00000614922.1

Frequencies

GnomAD3 genomes AF: 0.0143 AC: 2183 AN: 152138 Hom.: 39 Cov.: 31

Gnomad AFR AF: 0.00352

Gnomad AMI AF: 0.124

Gnomad AMR AF: 0.00772

Gnomad ASJ AF: 0.0701

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.0403

Gnomad FIN AF: 0.0103

Gnomad MID AF: 0.0222

Gnomad NFE AF: 0.0181

Gnomad OTH AF: 0.00958

GnomAD2 exomes AF: 0.0183 AC: 4592 AN: 251378 AF XY: 0.0200

Gnomad AFR exome AF: 0.00314

Gnomad AMR exome AF: 0.00532

Gnomad ASJ exome AF: 0.0601

Gnomad EAS exome AF: 0.000109

Gnomad FIN exome AF: 0.0115

Gnomad NFE exome AF: 0.0207

Gnomad OTH exome AF: 0.0196

GnomAD4 exome AF: 0.0177 AC: 25835 AN: 1461814 Hom.: 354 Cov.: 33 AF XY: 0.0187 AC XY: 13563 AN XY: 727218

African (AFR) AF: 0.00248 AC: 83 AN: 33478

American (AMR) AF: 0.00610 AC: 273 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.0633 AC: 1653 AN: 26134

East Asian (EAS) AF: 0.0000252 AC: 1 AN: 39696

South Asian (SAS) AF: 0.0345 AC: 2974 AN: 86256

European-Finnish (FIN) AF: 0.0111 AC: 594 AN: 53416

Middle Eastern (MID) AF: 0.0253 AC: 146 AN: 5768

European-Non Finnish (NFE) AF: 0.0171 AC: 18975 AN: 1111946

Other (OTH) AF: 0.0188 AC: 1136 AN: 60396

GnomAD4 genome AF: 0.0143 AC: 2180 AN: 152256 Hom.: 39 Cov.: 31 AF XY: 0.0143 AC XY: 1061 AN XY: 74454

African (AFR) AF: 0.00351 AC: 146 AN: 41546

American (AMR) AF: 0.00771 AC: 118 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.0701 AC: 243 AN: 3468

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5176

South Asian (SAS) AF: 0.0399 AC: 192 AN: 4810

European-Finnish (FIN) AF: 0.0103 AC: 109 AN: 10618

Middle Eastern (MID) AF: 0.0204 AC: 6 AN: 294

European-Non Finnish (NFE) AF: 0.0181 AC: 1232 AN: 68020

Other (OTH) AF: 0.00948 AC: 20 AN: 2110

Alfa AF: 0.0185 Hom.: 98

Bravo AF: 0.0133

TwinsUK AF: 0.0148 AC: 55

ALSPAC AF: 0.0145 AC: 56

ESP6500AA AF: 0.00477 AC: 21

ESP6500EA AF: 0.0174 AC: 150

ExAC AF: 0.0193 AC: 2342

Asia WGS AF: 0.0130 AC: 45 AN: 3478

EpiCase AF: 0.0192

EpiControl AF: 0.0212

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	BODY MASS INDEX QUANTITATIVE TRAIT LOCUS 10 (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.50	T
BayesDel_noAF	Benign	-0.47
CADD	Benign	23
DANN	Uncertain	1.0
DEOGEN2	Benign	0.051	T
Eigen	Benign	-0.028
Eigen_PC	Benign	0.091
FATHMM_MKL	Benign	0.54	D
LIST_S2	Benign	0.79	T
MetaRNN	Benign	0.0023	T
MetaSVM	Benign	-0.73	T
MutationAssessor	Benign	2.0	M
PhyloP100		1.8
PrimateAI	Benign	0.42	T
PROVEAN	Benign	-1.8	N
REVEL	Benign	0.20
Sift	Benign	0.053	T
Sift4G	Benign	0.15	T
Polyphen		0.070	B
Vest4		0.11
MPC		0.77
ClinPred		0.013	T
GERP RS		5.0
Varity_R		0.12
gMVP		0.62
Mutation Taster		=85/15	polymorphism (auto)

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

Other links and lift over

dbSNP: rs116454156; hg19: chr10-95347041; COSMIC: COSV65160232; COSMIC: COSV65160232;