NM_001195755.2:c.114G>A

Variant names:

• chr10-93566834-G-A
• rs139357642
• NM_001195755.2:c.114G>A

Variant summary

Our verdict is Benign. The variant received -11 ACMG points: 0P and 11B. BP4_Strong BP6_Moderate BP7 BS2

The NM_001195755.2(FFAR4):​c.114G>A​(p.Val38Val) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00287 in 1,601,242 control chromosomes in the GnomAD database, including 12 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0024 (0 hom., cov: 33)
  • Exomes 𝑓: 0.0029 (12 hom.)
• Consequence: FFAR4 NM_001195755.2 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.444
• Publications: 2 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 -11 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.58).
• BP6: Variant 10-93566834-G-A is Benign according to our data. Variant chr10-93566834-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 2640700.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=0.444 with no splicing effect.
• BS2: High Homozygotes in GnomAdExome4 at 12 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FFAR4	NM_001195755.2	c.114G>A	p.Val38Val	synonymous_variant	Exon 1 of 3	ENST00000371481.9	NP_001182684.1
FFAR4	NM_181745.4	c.114G>A	p.Val38Val	synonymous_variant	Exon 1 of 4		NP_859529.2
FFAR4	XM_011539746.4	c.114G>A	p.Val38Val	synonymous_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.114G>A	p.Val38Val	synonymous_variant	Exon 1 of 3	1	NM_001195755.2	ENSP00000360536.5
FFAR4	ENST00000371483.8	c.114G>A	p.Val38Val	synonymous_variant	Exon 1 of 4	1		ENSP00000360538.4
FFAR4	ENST00000604414.1	c.114G>A	p.Val38Val	synonymous_variant	Exon 1 of 3	3		ENSP00000474477.1

Frequencies

GnomAD3 genomes AF: 0.00235 AC: 358 AN: 152222 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.000386

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00196

Gnomad ASJ AF: 0.00288

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00198

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00410

Gnomad OTH AF: 0.000956

GnomAD2 exomes AF: 0.00237 AC: 525 AN: 221180 AF XY: 0.00226

Gnomad AFR exome AF: 0.000223

Gnomad AMR exome AF: 0.000912

Gnomad ASJ exome AF: 0.00284

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00279

Gnomad NFE exome AF: 0.00407

Gnomad OTH exome AF: 0.00271

GnomAD4 exome AF: 0.00293 AC: 4242 AN: 1448902 Hom.: 12 Cov.: 32 AF XY: 0.00288 AC XY: 2077 AN XY: 720364

African (AFR) AF: 0.000422 AC: 14 AN: 33138

American (AMR) AF: 0.000959 AC: 42 AN: 43798

Ashkenazi Jewish (ASJ) AF: 0.00247 AC: 64 AN: 25882

East Asian (EAS) AF: 0.00 AC: 0 AN: 38996

South Asian (SAS) AF: 0.0000944 AC: 8 AN: 84722

European-Finnish (FIN) AF: 0.00332 AC: 163 AN: 49136

Middle Eastern (MID) AF: 0.000347 AC: 2 AN: 5756

European-Non Finnish (NFE) AF: 0.00346 AC: 3827 AN: 1107616

Other (OTH) AF: 0.00204 AC: 122 AN: 59858

GnomAD4 genome AF: 0.00235 AC: 358 AN: 152340 Hom.: 0 Cov.: 33 AF XY: 0.00208 AC XY: 155 AN XY: 74482

African (AFR) AF: 0.000385 AC: 16 AN: 41584

American (AMR) AF: 0.00196 AC: 30 AN: 15314

Ashkenazi Jewish (ASJ) AF: 0.00288 AC: 10 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5166

South Asian (SAS) AF: 0.00 AC: 0 AN: 4828

European-Finnish (FIN) AF: 0.00198 AC: 21 AN: 10630

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00410 AC: 279 AN: 68028

Other (OTH) AF: 0.000946 AC: 2 AN: 2114

Alfa AF: 0.00313 Hom.: 0

Bravo AF: 0.00207

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Oct 01, 2022

CeGaT Center for Human Genetics Tuebingen

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

FFAR4: BP4, BP7 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.58
CADD	Benign	5.2
DANN	Benign	0.78
PhyloP100		0.44
PromoterAI		-0.010	Neutral
Mutation Taster		=100/0	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: rs139357642; hg19: chr10-95326591;