chr10-93579168-C-T

Variant names:

• chr10-93579168-C-T
• rs2058184736
• ENST00000371483.8:c.706C>T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_181745.4(FFAR4):​c.706C>T​(p.His236Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000274 in 1,461,806 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 17/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000027 (0 hom.)
• Consequence: FFAR4 NM_181745.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.599
• 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: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.07196191).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_181745.4. 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.696+2949C>T		intron	N/A	NP_001182684.1	Q5NUL3-2
	FFAR4	NM_181745.4		c.706C>T	p.His236Tyr	missense	Exon 3 of 4	NP_859529.2	Q5NUL3-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FFAR4	ENST00000371483.8	TSL:1	c.706C>T	p.His236Tyr	missense	Exon 3 of 4	ENSP00000360538.4	Q5NUL3-1
	FFAR4	ENST00000371481.9	TSL:1 MANE Select	c.696+2949C>T		intron	N/A	ENSP00000360536.5	Q5NUL3-2
	FFAR4	ENST00000944863.1		c.568-8052C>T		intron	N/A	ENSP00000614922.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000274 AC: 4 AN: 1461806 Hom.: 0 Cov.: 30 AF XY: 0.00000413 AC XY: 3 AN XY: 727214

African (AFR) AF: 0.00 AC: 0 AN: 33478

American (AMR) AF: 0.00 AC: 0 AN: 44720

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86256

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53418

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.00000360 AC: 4 AN: 1111942

Other (OTH) AF: 0.00 AC: 0 AN: 60388

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.26	T
BayesDel_noAF	Benign	-0.61
CADD	Benign	1.3
DANN	Benign	0.56
DEOGEN2	Benign	0.048	T
Eigen	Benign	-1.0
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.022	N
LIST_S2	Benign	0.36	T
M_CAP	Benign	0.017	T
MetaRNN	Benign	0.072	T
MetaSVM	Benign	-0.90	T
MutationAssessor	Benign	-0.34	N
PhyloP100		-0.60
PrimateAI	Benign	0.28	T
PROVEAN	Benign	-0.64	N
REVEL	Benign	0.13
Sift	Benign	0.12	T
Sift4G	Benign	0.45	T
Polyphen		0.0030	B
Vest4		0.23
MVP		0.46
MPC		0.64
ClinPred		0.089	T
GERP RS		-0.51
Varity_R		0.059
gMVP		0.38
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: rs2058184736; hg19: chr10-95338925;