chr10-93567243-G-A

Variant names:

• chr10-93567243-G-A
• rs1454563281
• NM_001195755.2:c.523G>A

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2 BP4_Strong BP6_Moderate

The NM_001195755.2(FFAR4):​c.523G>A​(p.Val175Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000897 in 1,448,778 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 Likely benign (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000090 (0 hom.)
• Consequence: FFAR4 NM_001195755.2 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.350

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

Verdict is Likely_benign. Variant got -4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.024678797).
• BP6: Variant 10-93567243-G-A is Benign according to our data. Variant chr10-93567243-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 3514799.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FFAR4	NM_001195755.2	c.523G>A	p.Val175Ile	missense_variant	Exon 1 of 3	ENST00000371481.9	NP_001182684.1
FFAR4	NM_181745.4	c.523G>A	p.Val175Ile	missense_variant	Exon 1 of 4		NP_859529.2
FFAR4	XM_011539746.4	c.523G>A	p.Val175Ile	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.523G>A	p.Val175Ile	missense_variant	Exon 1 of 3	1	NM_001195755.2	ENSP00000360536.5
FFAR4	ENST00000371483.8	c.523G>A	p.Val175Ile	missense_variant	Exon 1 of 4	1		ENSP00000360538.4
FFAR4	ENST00000604414.1	c.523G>A	p.Val175Ile	missense_variant	Exon 1 of 3	3		ENSP00000474477.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000897 AC: 13 AN: 1448778 Hom.: 0 Cov.: 33 AF XY: 0.00000832 AC XY: 6 AN XY: 721258

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000540

Gnomad4 OTH exome AF: 0.0000332

GnomAD4 genome Cov.: 32

EpiCase AF: 0.0000545

EpiControl AF: 0.00

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Aug 27, 2024

Ambry Genetics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.082
BayesDel_addAF	Benign	-0.24	T
BayesDel_noAF	Benign	-0.58
CADD	Benign	6.1
DANN	Benign	0.74
DEOGEN2	Benign	0.024	.;T;.
Eigen	Benign	-1.1
Eigen_PC	Benign	-0.95
FATHMM_MKL	Benign	0.20	N
LIST_S2	Benign	0.74	T;T;T
M_CAP	Benign	0.034	D
MetaRNN	Benign	0.025	T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.41	N;N;.
PrimateAI	Uncertain	0.56	T
PROVEAN	Benign	0.22	N;N;.
REVEL	Benign	0.062
Sift	Benign	1.0	T;T;.
Sift4G	Benign	0.80	T;T;T
Polyphen		0.0030	B;B;.
Vest4		0.053
MVP		0.33
MPC		0.42
ClinPred		0.038	T
GERP RS		0.33
Varity_R		0.048
gMVP		0.12

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

Publications

LitVar

Other links and lift over

dbSNP: rs1454563281; hg19: chr10-95327000; COSMIC: COSV65178491;