rs143911724

Variant names:

• chr10-93566914-T-C
• rs143911724
• NM_001195755.2:c.194T>C

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_001195755.2(FFAR4):​c.194T>C​(p.Val65Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000149 in 1,608,976 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000092 (0 hom., cov: 33)
  • Exomes 𝑓: 0.0000069 (0 hom.)
• Consequence: FFAR4 NM_001195755.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.725
• Publications: 0 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: Likely_benign. The variant received -2 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.11697921).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FFAR4	NM_001195755.2	c.194T>C	p.Val65Ala	missense_variant	Exon 1 of 3	ENST00000371481.9	NP_001182684.1
FFAR4	NM_181745.4	c.194T>C	p.Val65Ala	missense_variant	Exon 1 of 4		NP_859529.2
FFAR4	XM_011539746.4	c.194T>C	p.Val65Ala	missense_variant	Exon 1 of 3		XP_011538048.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FFAR4	ENST00000371481.9	c.194T>C	p.Val65Ala	missense_variant	Exon 1 of 3	1	NM_001195755.2	ENSP00000360536.5
FFAR4	ENST00000371483.8	c.194T>C	p.Val65Ala	missense_variant	Exon 1 of 4	1		ENSP00000360538.4
FFAR4	ENST00000604414.1	c.194T>C	p.Val65Ala	missense_variant	Exon 1 of 3	3		ENSP00000474477.1

Frequencies

GnomAD3 genomes AF: 0.0000920 AC: 14 AN: 152106 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.0000724

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000654

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.000478

GnomAD2 exomes AF: 0.0000125 AC: 3 AN: 240702 AF XY: 0.0000229

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000586

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.000169

GnomAD4 exome AF: 0.00000686 AC: 10 AN: 1456752 Hom.: 0 Cov.: 32 AF XY: 0.00000414 AC XY: 3 AN XY: 724756

African (AFR) AF: 0.00 AC: 0 AN: 33376

American (AMR) AF: 0.000113 AC: 5 AN: 44324

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26046

East Asian (EAS) AF: 0.00 AC: 0 AN: 39508

South Asian (SAS) AF: 0.0000117 AC: 1 AN: 85754

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 51034

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5762

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1110732

Other (OTH) AF: 0.0000664 AC: 4 AN: 60216

GnomAD4 genome AF: 0.0000920 AC: 14 AN: 152224 Hom.: 0 Cov.: 33 AF XY: 0.000121 AC XY: 9 AN XY: 74432

African (AFR) AF: 0.0000722 AC: 3 AN: 41534

American (AMR) AF: 0.000653 AC: 10 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5160

South Asian (SAS) AF: 0.00 AC: 0 AN: 4820

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10614

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 292

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68004

Other (OTH) AF: 0.000473 AC: 1 AN: 2114

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.000193

ExAC AF: 0.00000826 AC: 1

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Oct 31, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.194T>C (p.V65A) alteration is located in exon 1 (coding exon 1) of the FFAR4 gene. This alteration results from a T to C substitution at nucleotide position 194, causing the valine (V) at amino acid position 65 to be replaced by an alanine (A). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.18
BayesDel_addAF	Benign	-0.28	T
BayesDel_noAF	Benign	-0.46
CADD	Uncertain	24
DANN	Uncertain	0.99
DEOGEN2	Benign	0.33	.;T;.
Eigen	Benign	-0.080
Eigen_PC	Benign	0.068
FATHMM_MKL	Benign	0.58	D
LIST_S2	Benign	0.74	T;T;T
M_CAP	Benign	0.014	T
MetaRNN	Benign	0.12	T;T;T
MetaSVM	Benign	-0.97	T
MutationAssessor	Uncertain	2.3	M;M;.
PhyloP100		0.72
PrimateAI	Uncertain	0.77	T
PROVEAN	Uncertain	-2.9	D;D;.
REVEL	Benign	0.10
Sift	Uncertain	0.016	D;D;.
Sift4G	Uncertain	0.022	D;D;D
Polyphen		0.0050	B;B;.
Vest4		0.22
MVP		0.66
MPC		1.3
ClinPred		0.95	D
GERP RS		5.2
PromoterAI		0.037	Neutral
Varity_R		0.35
gMVP		0.37
Mutation Taster		=88/12	polymorphism

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: rs143911724; hg19: chr10-95326671;