rs73931123

Variant names:

• chr19-35449850-A-G
• rs73931123
• NM_001370087.1:c.136A>G

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_005306.3(FFAR2):​c.136A>G​(p.Ile46Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00146 in 1,613,832 control chromosomes in the GnomAD database, including 33 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0078 (10 hom., cov: 32)
  • Exomes 𝑓: 0.00080 (23 hom.)
• Consequence: FFAR2 NM_005306.3 missense
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.63
• Publications: 1 publications found

Genes affected

FFAR2 (HGNC:4501): (free fatty acid receptor 2) This gene encodes a member of the GP40 family of G protein-coupled receptors that are clustered together on chromosome 19. The encoded protein is a receptor for short chain free fatty acids and may be involved in the inflammatory response and in regulating lipid plasma levels. [provided by RefSeq, Apr 2009]

ACMG classification

Our verdict: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0073796213).
• BP6: Variant 19-35449850-A-G is Benign according to our data. Variant chr19-35449850-A-G is described in ClinVar as Benign. ClinVar VariationId is 791358.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00779 (1186/152312) while in subpopulation AFR AF = 0.0275 (1143/41580). AF 95% confidence interval is 0.0262. There are 10 homozygotes in GnomAd4. There are 582 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 10 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005306.3. 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
	FFAR2	NM_001370087.1	MANE Select	c.136A>G	p.Ile46Val	missense	Exon 2 of 2	NP_001357016.1
	FFAR2	NM_005306.3		c.136A>G	p.Ile46Val	missense	Exon 3 of 3	NP_005297.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FFAR2	ENST00000599180.3	TSL:1 MANE Select	c.136A>G	p.Ile46Val	missense	Exon 2 of 2	ENSP00000473159.1
	FFAR2	ENST00000246549.2	TSL:6	c.136A>G	p.Ile46Val	missense	Exon 1 of 1	ENSP00000246549.2
	FFAR2	ENST00000601590.1	TSL:5	n.17-1303A>G		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.00779 AC: 1186 AN: 152194 Hom.: 10 Cov.: 32

Gnomad AFR AF: 0.0275

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00196

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000294

Gnomad OTH AF: 0.00525

GnomAD2 exomes AF: 0.00208 AC: 522 AN: 250930 AF XY: 0.00154

Gnomad AFR exome AF: 0.0293

Gnomad AMR exome AF: 0.00113

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000176

Gnomad OTH exome AF: 0.000653

GnomAD4 exome AF: 0.000801 AC: 1170 AN: 1461520 Hom.: 23 Cov.: 32 AF XY: 0.000685 AC XY: 498 AN XY: 727098

African (AFR) AF: 0.0302 AC: 1012 AN: 33480

American (AMR) AF: 0.00127 AC: 57 AN: 44724

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

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

South Asian (SAS) AF: 0.0000232 AC: 2 AN: 86248

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53074

Middle Eastern (MID) AF: 0.00173 AC: 10 AN: 5768

European-Non Finnish (NFE) AF: 0.0000144 AC: 16 AN: 1112002

Other (OTH) AF: 0.00121 AC: 73 AN: 60388

GnomAD4 genome AF: 0.00779 AC: 1186 AN: 152312 Hom.: 10 Cov.: 32 AF XY: 0.00781 AC XY: 582 AN XY: 74476

African (AFR) AF: 0.0275 AC: 1143 AN: 41580

American (AMR) AF: 0.00190 AC: 29 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5180

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4828

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10608

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

European-Non Finnish (NFE) AF: 0.0000294 AC: 2 AN: 68020

Other (OTH) AF: 0.00520 AC: 11 AN: 2116

Alfa AF: 0.00294 Hom.: 8

Bravo AF: 0.00882

ESP6500AA AF: 0.0277 AC: 122

ESP6500EA AF: 0.00 AC: 0

ExAC AF: 0.00266 AC: 323

Asia WGS AF: 0.00144 AC: 5 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, single submitter

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.14
BayesDel_addAF	Benign	-0.45	T
BayesDel_noAF	Benign	-0.39
CADD	Benign	20
DANN	Uncertain	1.0
DEOGEN2	Benign	0.031	T
Eigen	Uncertain	0.41
Eigen_PC	Uncertain	0.46
FATHMM_MKL	Uncertain	0.92	D
LIST_S2	Benign	0.74	T
MetaRNN	Benign	0.0074	T
MetaSVM	Benign	-0.73	T
MutationAssessor	Benign	1.8	L
PhyloP100		1.6
PrimateAI	Uncertain	0.59	T
PROVEAN	Benign	-0.51	N
REVEL	Benign	0.25
Sift	Benign	0.45	T
Sift4G	Benign	0.61	T
Polyphen		0.91	P
Vest4		0.12
MVP		0.80
MPC		0.34
ClinPred		0.066	T
GERP RS		5.8
PromoterAI		-0.00010	Neutral
Varity_R		0.12
gMVP		0.12
Mutation Taster		=89/11	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: rs73931123; hg19: chr19-35940752;