10-93587293-A-G

Position:

• chr10-93587293-A-G

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_001195755.2(FFAR4):​c.770A>G​(p.Gln257Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00289 in 1,614,122 control chromosomes in the GnomAD database, including 109 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0052 (20 hom., cov: 31)
  • Exomes 𝑓: 0.0027 (89 hom.)
• Consequence: FFAR4 NM_001195755.2 missense
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.77

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 Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0024080873).
• BP6: Variant 10-93587293-A-G is Benign according to our data. Variant chr10-93587293-A-G is described in ClinVar as [Benign]. Clinvar id is 708083.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population eas. gnomad4 allele frequency = 0.00521 (793/152268) while in subpopulation EAS AF= 0.0219 (113/5166). AF 95% confidence interval is 0.0186. There are 20 homozygotes in gnomad4. There are 567 alleles in male gnomad4 subpopulation. Median coverage is 31. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 20 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FFAR4	NM_001195755.2	c.770A>G	p.Gln257Arg	missense_variant	3/3	ENST00000371481.9	NP_001182684.1
FFAR4	NM_181745.4	c.818A>G	p.Gln273Arg	missense_variant	4/4		NP_859529.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FFAR4	ENST00000371481.9	c.770A>G	p.Gln257Arg	missense_variant	3/3	1	NM_001195755.2	ENSP00000360536.5
FFAR4	ENST00000371483.8	c.818A>G	p.Gln273Arg	missense_variant	4/4	1		ENSP00000360538.4
FFAR4	ENST00000604414.1	c.696+11074A>G		intron_variant		3		ENSP00000474477.1

Frequencies

GnomAD3 genomes AF: 0.00521 AC: 792 AN: 152150 Hom.: 20 Cov.: 31

Gnomad AFR AF: 0.000314

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00105

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.0218

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.0546

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000867

Gnomad OTH AF: 0.00479

GnomAD3 exomes AF: 0.00614 AC: 1545 AN: 251430 Hom.: 30 AF XY: 0.00601 AC XY: 817 AN XY: 135884

Gnomad AFR exome AF: 0.000246

Gnomad AMR exome AF: 0.000116

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0228

Gnomad SAS exome AF: 0.000457

Gnomad FIN exome AF: 0.0445

Gnomad NFE exome AF: 0.000994

Gnomad OTH exome AF: 0.00440

GnomAD4 exome AF: 0.00265 AC: 3879 AN: 1461854 Hom.: 89 Cov.: 33 AF XY: 0.00259 AC XY: 1884 AN XY: 727224

Gnomad4 AFR exome AF: 0.000239

Gnomad4 AMR exome AF: 0.000112

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0277

Gnomad4 SAS exome AF: 0.000359

Gnomad4 FIN exome AF: 0.0410

Gnomad4 NFE exome AF: 0.000266

Gnomad4 OTH exome AF: 0.00399

GnomAD4 genome AF: 0.00521 AC: 793 AN: 152268 Hom.: 20 Cov.: 31 AF XY: 0.00761 AC XY: 567 AN XY: 74466

Gnomad4 AFR AF: 0.000313

Gnomad4 AMR AF: 0.00105

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.0219

Gnomad4 SAS AF: 0.000207

Gnomad4 FIN AF: 0.0546

Gnomad4 NFE AF: 0.000867

Gnomad4 OTH AF: 0.00522

Alfa AF: 0.00132 Hom.: 6

Bravo AF: 0.00159

ESP6500AA AF: 0.000454 AC: 2

ESP6500EA AF: 0.000349 AC: 3

ExAC AF: 0.00553 AC: 672

Asia WGS AF: 0.0140 AC: 50 AN: 3478

EpiCase AF: 0.000327

EpiControl AF: 0.000237

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Dec 01, 2017

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.080
BayesDel_addAF	Benign	-0.68	T
BayesDel_noAF	Benign	-0.73
CADD	Benign	19
DANN	Benign	0.71
DEOGEN2	Benign	0.018	.;T
Eigen	Benign	-0.61
Eigen_PC	Benign	-0.37
FATHMM_MKL	Benign	0.68	D
LIST_S2	Benign	0.61	T;T
MetaRNN	Benign	0.0024	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-0.13	.;N
PrimateAI	Benign	0.41	T
PROVEAN	Benign	0.030	N;N
REVEL	Benign	0.069
Sift	Benign	1.0	T;T
Sift4G	Benign	0.84	T;T
Polyphen		0.0	B;B
Vest4		0.045
MVP		0.32
MPC		0.57
ClinPred		0.013	T
GERP RS		3.9
Varity_R		0.12
gMVP		0.49

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: rs115724324; hg19: chr10-95347050; COSMIC: COSV65159754; COSMIC: COSV65159754;