7-141778774-G-C

Position:

• chr7-141778774-G-C

Variant summary

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

The NM_016944.2(TAS2R4):​c.286G>C​(p.Val96Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.501 in 1,613,840 control chromosomes in the GnomAD database, including 205,170 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 0.47 (17453 hom., cov: 32)
  • Exomes 𝑓: 0.50 (187717 hom.)
• Consequence: TAS2R4 NM_016944.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0500

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=1.7966802E-5).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.732 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TAS2R4	NM_016944.2	c.286G>C	p.Val96Leu	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.286G>C	p.Val96Leu	missense_variant	1/1	6	NM_016944.2	ENSP00000247881.3
SSBP1	ENST00000465582.5	c.*31-8949G>C		intron_variant		5		ENSP00000420485.1

Frequencies

GnomAD3 genomes AF: 0.473 AC: 71818 AN: 151850 Hom.: 17427 Cov.: 32

Gnomad AFR AF: 0.367

Gnomad AMI AF: 0.241

Gnomad AMR AF: 0.530

Gnomad ASJ AF: 0.470

Gnomad EAS AF: 0.752

Gnomad SAS AF: 0.593

Gnomad FIN AF: 0.482

Gnomad MID AF: 0.516

Gnomad NFE AF: 0.496

Gnomad OTH AF: 0.485

GnomAD3 exomes AF: 0.520 AC: 130855 AN: 251460 Hom.: 35088 AF XY: 0.525 AC XY: 71318 AN XY: 135914

Gnomad AFR exome AF: 0.359

Gnomad AMR exome AF: 0.543

Gnomad ASJ exome AF: 0.464

Gnomad EAS exome AF: 0.754

Gnomad SAS exome AF: 0.583

Gnomad FIN exome AF: 0.481

Gnomad NFE exome AF: 0.494

Gnomad OTH exome AF: 0.521

GnomAD4 exome AF: 0.504 AC: 736128 AN: 1461868 Hom.: 187717 Cov.: 79 AF XY: 0.507 AC XY: 368827 AN XY: 727236

Gnomad4 AFR exome AF: 0.358

Gnomad4 AMR exome AF: 0.546

Gnomad4 ASJ exome AF: 0.460

Gnomad4 EAS exome AF: 0.770

Gnomad4 SAS exome AF: 0.585

Gnomad4 FIN exome AF: 0.483

Gnomad4 NFE exome AF: 0.492

Gnomad4 OTH exome AF: 0.512

GnomAD4 genome AF: 0.473 AC: 71890 AN: 151972 Hom.: 17453 Cov.: 32 AF XY: 0.477 AC XY: 35463 AN XY: 74278

Gnomad4 AFR AF: 0.367

Gnomad4 AMR AF: 0.530

Gnomad4 ASJ AF: 0.470

Gnomad4 EAS AF: 0.751

Gnomad4 SAS AF: 0.594

Gnomad4 FIN AF: 0.482

Gnomad4 NFE AF: 0.496

Gnomad4 OTH AF: 0.489

Alfa AF: 0.497 Hom.: 14218

Bravo AF: 0.473

TwinsUK AF: 0.494 AC: 1830

ALSPAC AF: 0.481 AC: 1852

ESP6500AA AF: 0.357 AC: 1575

ESP6500EA AF: 0.497 AC: 4274

ExAC AF: 0.517 AC: 62722

Asia WGS AF: 0.669 AC: 2326 AN: 3478

EpiCase AF: 0.504

EpiControl AF: 0.503

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.081
BayesDel_addAF	Benign	-0.78	T
BayesDel_noAF	Benign	-0.74
CADD	Benign	7.8
DANN	Benign	0.50
DEOGEN2	Benign	0.00036	T
Eigen	Benign	-1.4
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.0032	N
LIST_S2	Benign	0.23	T
MetaRNN	Benign	0.000018	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	-1.4	N
PrimateAI	Benign	0.33	T
PROVEAN	Benign	1.3	N
REVEL	Benign	0.048
Sift	Benign	1.0	T
Sift4G	Benign	1.0	T
Polyphen		0.0010	B
Vest4		0.010
MPC		0.075
ClinPred		0.0034	T
GERP RS		2.7
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.8
Varity_R		0.053
gMVP		0.044

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: rs2234001; hg19: chr7-141478574; COSMIC: COSV56093719;