7-141778774-G-C

Variant names:

• chr7-141778774-G-C
• rs2234001
• NM_016944.2:c.286G>C

Variant summary

Our verdict is Benign. The variant received -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. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• 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
• Publications: 60 publications found

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]

SSBP1 Gene-Disease associations (from GenCC):

• optic atrophy 13 with retinal and foveal abnormalities

  Inheritance: AD Classification: STRONG, MODERATE Submitted by: ClinGen, Ambry Genetics
• Leigh syndrome

  Inheritance: AD Classification: LIMITED Submitted by: ClinGen

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_016944.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TAS2R4	NM_016944.2	MANE Select	c.286G>C	p.Val96Leu	missense	Exon 1 of 1	NP_058640.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TAS2R4	ENST00000247881.4	TSL:6 MANE Select	c.286G>C	p.Val96Leu	missense	Exon 1 of 1	ENSP00000247881.3
	SSBP1	ENST00000465582.5	TSL:5	c.*31-8949G>C		intron	N/A	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

GnomAD2 exomes AF: 0.520 AC: 130855 AN: 251460 AF XY: 0.525

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 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

African (AFR) AF: 0.358 AC: 11991 AN: 33480

American (AMR) AF: 0.546 AC: 24422 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.460 AC: 12034 AN: 26136

East Asian (EAS) AF: 0.770 AC: 30562 AN: 39700

South Asian (SAS) AF: 0.585 AC: 50464 AN: 86256

European-Finnish (FIN) AF: 0.483 AC: 25784 AN: 53414

Middle Eastern (MID) AF: 0.505 AC: 2913 AN: 5768

European-Non Finnish (NFE) AF: 0.492 AC: 547042 AN: 1111994

Other (OTH) AF: 0.512 AC: 30916 AN: 60396

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

African (AFR) AF: 0.367 AC: 15218 AN: 41446

American (AMR) AF: 0.530 AC: 8092 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.470 AC: 1631 AN: 3470

East Asian (EAS) AF: 0.751 AC: 3885 AN: 5170

South Asian (SAS) AF: 0.594 AC: 2860 AN: 4816

European-Finnish (FIN) AF: 0.482 AC: 5086 AN: 10546

Middle Eastern (MID) AF: 0.517 AC: 152 AN: 294

European-Non Finnish (NFE) AF: 0.496 AC: 33715 AN: 67934

Other (OTH) AF: 0.489 AC: 1033 AN: 2112

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 v4.9

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
PhyloP100		0.050
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
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: rs2234001; hg19: chr7-141478574; COSMIC: COSV56093719;