7-122994970-C-T

Variant names:

• chr7-122994970-C-T
• rs860170
• NM_016945.3:c.665G>A

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP6 BA1

The NM_016945.3(TAS2R16):​c.665G>A​(p.Arg222His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.686 in 1,613,532 control chromosomes in the GnomAD database, including 382,313 homozygotes. 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 Benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.74 (42587 hom., cov: 31)
  • Exomes 𝑓: 0.68 (339726 hom.)
• Consequence: TAS2R16 NM_016945.3 missense
• Clinical Significance: Benign no assertion criteria provided B:1
• Conservation: PhyloP100: 1.56
• Publications: 54 publications found

Genes affected

TAS2R16 (HGNC:14921): (taste 2 receptor member 16) This gene encodes a member of a family of candidate taste receptors that are members of the G protein-coupled receptor superfamily. These family members are specifically expressed by taste receptor cells of the tongue and palate epithelia. Each of these apparently intronless genes encodes a 7-transmembrane receptor protein, functioning as a bitter taste receptor. This gene is clustered with another 3 candidate taste receptor genes in chromosome 7 and is genetically linked to loci that influence bitter perception. [provided by RefSeq, Jul 2008]

ACMG classification

Our verdict: Benign. The variant received -13 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=3.3664874E-6).
• BP6: Variant 7-122994970-C-T is Benign according to our data. Variant chr7-122994970-C-T is described in ClinVar as Benign. ClinVar VariationId is 3058839.Status of the report is no_assertion_criteria_provided, 0 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.897 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TAS2R16	NM_016945.3	c.665G>A	p.Arg222His	missense_variant	Exon 1 of 1	ENST00000249284.3	NP_058641.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TAS2R16	ENST00000249284.3	c.665G>A	p.Arg222His	missense_variant	Exon 1 of 1	6	NM_016945.3	ENSP00000249284.2

Frequencies

GnomAD3 genomes AF: 0.739 AC: 112275 AN: 151852 Hom.: 42517 Cov.: 31

Gnomad AFR AF: 0.904

Gnomad AMI AF: 0.596

Gnomad AMR AF: 0.746

Gnomad ASJ AF: 0.683

Gnomad EAS AF: 0.531

Gnomad SAS AF: 0.670

Gnomad FIN AF: 0.657

Gnomad MID AF: 0.734

Gnomad NFE AF: 0.676

Gnomad OTH AF: 0.736

GnomAD2 exomes AF: 0.684 AC: 171207 AN: 250376 AF XY: 0.681

Gnomad AFR exome AF: 0.913

Gnomad AMR exome AF: 0.679

Gnomad ASJ exome AF: 0.685

Gnomad EAS exome AF: 0.532

Gnomad FIN exome AF: 0.650

Gnomad NFE exome AF: 0.682

Gnomad OTH exome AF: 0.676

GnomAD4 exome AF: 0.680 AC: 993779 AN: 1461560 Hom.: 339726 Cov.: 70 AF XY: 0.680 AC XY: 494303 AN XY: 727092

African (AFR) AF: 0.919 AC: 30732 AN: 33458

American (AMR) AF: 0.689 AC: 30820 AN: 44702

Ashkenazi Jewish (ASJ) AF: 0.687 AC: 17947 AN: 26112

East Asian (EAS) AF: 0.540 AC: 21441 AN: 39690

South Asian (SAS) AF: 0.692 AC: 59675 AN: 86242

European-Finnish (FIN) AF: 0.648 AC: 34584 AN: 53402

Middle Eastern (MID) AF: 0.747 AC: 4302 AN: 5758

European-Non Finnish (NFE) AF: 0.677 AC: 752805 AN: 1111808

Other (OTH) AF: 0.687 AC: 41473 AN: 60388

GnomAD4 genome AF: 0.740 AC: 112408 AN: 151972 Hom.: 42587 Cov.: 31 AF XY: 0.737 AC XY: 54723 AN XY: 74246

African (AFR) AF: 0.904 AC: 37544 AN: 41514

American (AMR) AF: 0.747 AC: 11382 AN: 15242

Ashkenazi Jewish (ASJ) AF: 0.683 AC: 2366 AN: 3466

East Asian (EAS) AF: 0.531 AC: 2721 AN: 5126

South Asian (SAS) AF: 0.671 AC: 3226 AN: 4806

European-Finnish (FIN) AF: 0.657 AC: 6932 AN: 10558

Middle Eastern (MID) AF: 0.724 AC: 213 AN: 294

European-Non Finnish (NFE) AF: 0.676 AC: 45921 AN: 67948

Other (OTH) AF: 0.740 AC: 1559 AN: 2106

Alfa AF: 0.696 Hom.: 171057

Bravo AF: 0.755

TwinsUK AF: 0.688 AC: 2551

ALSPAC AF: 0.693 AC: 2672

ESP6500AA AF: 0.904 AC: 3984

ESP6500EA AF: 0.677 AC: 5822

ExAC AF: 0.688 AC: 83485

Asia WGS AF: 0.678 AC: 2356 AN: 3478

EpiCase AF: 0.677

EpiControl AF: 0.675

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

Submissions by phenotype

TAS2R16-related disorder Benign:1

Oct 16, 2019

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.061
BayesDel_addAF	Benign	-0.77	T
BayesDel_noAF	Benign	-0.74
CADD	Benign	6.5
DANN	Benign	0.049
DEOGEN2	Benign	0.0082	T
Eigen	Benign	-1.5
Eigen_PC	Benign	-1.3
FATHMM_MKL	Benign	0.0036	N
LIST_S2	Benign	0.18	T
MetaRNN	Benign	0.0000034	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	-2.8	N
PhyloP100		1.6
PrimateAI	Benign	0.32	T
PROVEAN	Benign	7.2	N
REVEL	Benign	0.10
Sift	Benign	1.0	T
Sift4G	Benign	1.0	T
Polyphen		0.0	B
Vest4		0.029
MPC		0.011
ClinPred		0.0019	T
GERP RS		2.2
Varity_R		0.030
gMVP		0.089
Mutation Taster		=100/0	polymorphism (auto)

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: rs860170; hg19: chr7-122635024; COSMIC: COSV50798563;