7-141790438-G-T

Variant names:

• chr7-141790438-G-T
• rs2227264
• NM_018980.3:c.77G>T

Variant summary

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

The NM_018980.3(TAS2R5):​c.77G>T​(p.Ser26Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.482 in 1,613,890 control chromosomes in the GnomAD database, including 190,670 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 the same amino acid substitution has been previously reported as Likely benign in UniProt.

• Frequency:
  • Genomes: 𝑓 0.43 (15162 hom., cov: 32)
  • Exomes 𝑓: 0.49 (175508 hom.)
• Consequence: TAS2R5 NM_018980.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.383

Genes affected

TAS2R5 (HGNC:14912): (taste 2 receptor member 5) This gene encodes a bitter taste receptor; bitter taste receptors are members of the G protein-coupled receptor superfamily and are specifically expressed by taste receptor cells of the tongue and palate epithelia. Each of these apparently intronless taste receptor genes encodes a 7-transmembrane receptor protein, functioning as a bitter taste receptor. This gene is clustered with another 3 candidate taste receptor genes on chromosome 7 and is genetically linked to loci that influence bitter perception. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=2.5815077E-6).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.695 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TAS2R5	NM_018980.3	c.77G>T	p.Ser26Ile	missense_variant	Exon 1 of 1	ENST00000247883.5	NP_061853.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TAS2R5	ENST00000247883.5	c.77G>T	p.Ser26Ile	missense_variant	Exon 1 of 1	6	NM_018980.3	ENSP00000247883.4

Frequencies

GnomAD3 genomes AF: 0.434 AC: 65879 AN: 151932 Hom.: 15153 Cov.: 32

Gnomad AFR AF: 0.263

Gnomad AMI AF: 0.238

Gnomad AMR AF: 0.515

Gnomad ASJ AF: 0.468

Gnomad EAS AF: 0.715

Gnomad SAS AF: 0.441

Gnomad FIN AF: 0.462

Gnomad MID AF: 0.506

Gnomad NFE AF: 0.492

Gnomad OTH AF: 0.456

GnomAD3 exomes AF: 0.489 AC: 122895 AN: 251354 Hom.: 31303 AF XY: 0.490 AC XY: 66634 AN XY: 135860

Gnomad AFR exome AF: 0.254

Gnomad AMR exome AF: 0.532

Gnomad ASJ exome AF: 0.461

Gnomad EAS exome AF: 0.720

Gnomad SAS exome AF: 0.451

Gnomad FIN exome AF: 0.461

Gnomad NFE exome AF: 0.490

Gnomad OTH exome AF: 0.502

GnomAD4 exome AF: 0.487 AC: 711860 AN: 1461838 Hom.: 175508 Cov.: 59 AF XY: 0.488 AC XY: 354638 AN XY: 727218

Gnomad4 AFR exome AF: 0.253

Gnomad4 AMR exome AF: 0.535

Gnomad4 ASJ exome AF: 0.458

Gnomad4 EAS exome AF: 0.715

Gnomad4 SAS exome AF: 0.454

Gnomad4 FIN exome AF: 0.462

Gnomad4 NFE exome AF: 0.488

Gnomad4 OTH exome AF: 0.490

GnomAD4 genome AF: 0.434 AC: 65926 AN: 152052 Hom.: 15162 Cov.: 32 AF XY: 0.436 AC XY: 32443 AN XY: 74332

Gnomad4 AFR AF: 0.264

Gnomad4 AMR AF: 0.515

Gnomad4 ASJ AF: 0.468

Gnomad4 EAS AF: 0.715

Gnomad4 SAS AF: 0.442

Gnomad4 FIN AF: 0.462

Gnomad4 NFE AF: 0.492

Gnomad4 OTH AF: 0.462

Alfa AF: 0.488 Hom.: 38081

Bravo AF: 0.434

TwinsUK AF: 0.489 AC: 1813

ALSPAC AF: 0.478 AC: 1841

ESP6500AA AF: 0.255 AC: 1124

ESP6500EA AF: 0.493 AC: 4239

ExAC AF: 0.481 AC: 58437

Asia WGS AF: 0.560 AC: 1947 AN: 3478

EpiCase AF: 0.500

EpiControl AF: 0.498

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.075
BayesDel_addAF	Benign	-0.76	T
BayesDel_noAF	Benign	-0.72
CADD	Benign	1.0
DANN	Benign	0.77
DEOGEN2	Benign	0.0010	T
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.00016	N
LIST_S2	Benign	0.18	T
MetaRNN	Benign	0.0000026	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-0.34	N
PrimateAI	Benign	0.24	T
PROVEAN	Benign	2.2	N
REVEL	Benign	0.035
Sift	Benign	0.11	T
Sift4G	Benign	0.80	T
Polyphen		0.0	B
Vest4		0.040
MPC		0.082
ClinPred		0.0059	T
GERP RS		3.4
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.070
gMVP		0.073

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: rs2227264; hg19: chr7-141490238; COSMIC: COSV99078036; COSMIC: COSV99078036;