rs2233998

Positions:

• chr7-141778508-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_016944.2(TAS2R4):​c.20T>C​(p.Phe7Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.478 in 1,611,660 control chromosomes in the GnomAD database, including 187,191 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

• Frequency:
  • Genomes: 𝑓 0.42 (14547 hom., cov: 32)
  • Exomes 𝑓: 0.48 (172644 hom.)
• Consequence: TAS2R4 NM_016944.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.959

Genes affected

TAS2R4 (HGNC:14911): (taste 2 receptor member 4) This gene encodes a member of a family of candidate taste receptors that are members of the G protein-coupled receptor superfamily and that are specifically expressed by taste receptor cells of the tongue and palate epithelia. These apparently intronless genes encode 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]

SSBP1 (HGNC:11317): (single stranded DNA binding protein 1) SSBP1 is a housekeeping gene involved in mitochondrial biogenesis (Tiranti et al., 1995 [PubMed 7789991]). It is also a subunit of a single-stranded DNA (ssDNA)-binding complex involved in the maintenance of genome stability (Huang et al., 2009) [PubMed 19683501].[supplied by OMIM, Feb 2010]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=6.0810853E-6).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.667 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TAS2R4	NM_016944.2	c.20T>C	p.Phe7Ser	missense_variant	1/1	ENST00000247881.4	NP_058640.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TAS2R4	ENST00000247881.4	c.20T>C	p.Phe7Ser	missense_variant	1/1	6	NM_016944.2	ENSP00000247881.3
SSBP1	ENST00000465582.5	c.*31-9215T>C		intron_variant		5		ENSP00000420485.1

Frequencies

GnomAD3 genomes AF: 0.422 AC: 64080 AN: 151988 Hom.: 14540 Cov.: 32

Gnomad AFR AF: 0.233

Gnomad AMI AF: 0.242

Gnomad AMR AF: 0.492

Gnomad ASJ AF: 0.467

Gnomad EAS AF: 0.687

Gnomad SAS AF: 0.441

Gnomad FIN AF: 0.462

Gnomad MID AF: 0.497

Gnomad NFE AF: 0.492

Gnomad OTH AF: 0.449

GnomAD3 exomes AF: 0.479 AC: 119886 AN: 250364 Hom.: 29871 AF XY: 0.482 AC XY: 65293 AN XY: 135324

Gnomad AFR exome AF: 0.222

Gnomad AMR exome AF: 0.492

Gnomad ASJ exome AF: 0.457

Gnomad EAS exome AF: 0.691

Gnomad SAS exome AF: 0.450

Gnomad FIN exome AF: 0.461

Gnomad NFE exome AF: 0.490

Gnomad OTH exome AF: 0.492

GnomAD4 exome AF: 0.483 AC: 705611 AN: 1459552 Hom.: 172644 Cov.: 42 AF XY: 0.484 AC XY: 351725 AN XY: 725986

Gnomad4 AFR exome AF: 0.220

Gnomad4 AMR exome AF: 0.496

Gnomad4 ASJ exome AF: 0.453

Gnomad4 EAS exome AF: 0.675

Gnomad4 SAS exome AF: 0.453

Gnomad4 FIN exome AF: 0.462

Gnomad4 NFE exome AF: 0.488

Gnomad4 OTH exome AF: 0.485

GnomAD4 genome AF: 0.422 AC: 64117 AN: 152108 Hom.: 14547 Cov.: 32 AF XY: 0.424 AC XY: 31537 AN XY: 74352

Gnomad4 AFR AF: 0.233

Gnomad4 AMR AF: 0.491

Gnomad4 ASJ AF: 0.467

Gnomad4 EAS AF: 0.686

Gnomad4 SAS AF: 0.441

Gnomad4 FIN AF: 0.462

Gnomad4 NFE AF: 0.492

Gnomad4 OTH AF: 0.455

Alfa AF: 0.483 Hom.: 29227

Bravo AF: 0.418

TwinsUK AF: 0.490 AC: 1816

ALSPAC AF: 0.476 AC: 1836

ESP6500AA AF: 0.226 AC: 996

ESP6500EA AF: 0.492 AC: 4228

ExAC AF: 0.472 AC: 57270

Asia WGS AF: 0.551 AC: 1916 AN: 3478

EpiCase AF: 0.499

EpiControl AF: 0.498

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.78	T
BayesDel_noAF	Benign	-0.75
CADD	Benign	5.8
DANN	Benign	0.77
DEOGEN2	Benign	0.0017	T
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.14	N
LIST_S2	Benign	0.24	T
MetaRNN	Benign	0.0000061	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.4	L
PrimateAI	Benign	0.31	T
PROVEAN	Benign	-0.75	N
REVEL	Benign	0.032
Sift	Benign	0.14	T
Sift4G	Uncertain	0.042	D
Polyphen		0.0010	B
Vest4		0.050
MPC		0.14
ClinPred		0.010	T
GERP RS		1.6
Varity_R		0.12
gMVP		0.18

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: rs2233998; hg19: chr7-141478308; COSMIC: COSV56094064;