7-141778505-A-C

Position:

• chr7-141778505-A-C

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_016944.2(TAS2R4):​c.17A>C​(p.Tyr6Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00277 in 1,612,472 control chromosomes in the GnomAD database, including 141 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0064 (37 hom., cov: 32)
  • Exomes 𝑓: 0.0024 (104 hom.)
• Consequence: TAS2R4 NM_016944.2 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.582

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.007298559).
• BP6: Variant 7-141778505-A-C is Benign according to our data. Variant chr7-141778505-A-C is described in ClinVar as [Benign]. Clinvar id is 720426.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.0513 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TAS2R4	NM_016944.2	c.17A>C	p.Tyr6Ser	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.17A>C	p.Tyr6Ser	missense_variant	1/1	6	NM_016944.2	ENSP00000247881.3
SSBP1	ENST00000465582.5	c.*31-9218A>C		intron_variant		5		ENSP00000420485.1

Frequencies

GnomAD3 genomes AF: 0.00636 AC: 968 AN: 152190 Hom.: 36 Cov.: 32

Gnomad AFR AF: 0.00150

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0544

Gnomad ASJ AF: 0.000288

Gnomad EAS AF: 0.00769

Gnomad SAS AF: 0.00145

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000191

Gnomad OTH AF: 0.00717

GnomAD3 exomes AF: 0.00928 AC: 2324 AN: 250388 Hom.: 78 AF XY: 0.00720 AC XY: 974 AN XY: 135352

Gnomad AFR exome AF: 0.00160

Gnomad AMR exome AF: 0.0604

Gnomad ASJ exome AF: 0.000200

Gnomad EAS exome AF: 0.00729

Gnomad SAS exome AF: 0.000954

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000124

Gnomad OTH exome AF: 0.00656

GnomAD4 exome AF: 0.00240 AC: 3501 AN: 1460164 Hom.: 104 Cov.: 29 AF XY: 0.00212 AC XY: 1538 AN XY: 726308

Gnomad4 AFR exome AF: 0.000899

Gnomad4 AMR exome AF: 0.0568

Gnomad4 ASJ exome AF: 0.0000769

Gnomad4 EAS exome AF: 0.0165

Gnomad4 SAS exome AF: 0.00100

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000711

Gnomad4 OTH exome AF: 0.00189

GnomAD4 genome AF: 0.00636 AC: 968 AN: 152308 Hom.: 37 Cov.: 32 AF XY: 0.00768 AC XY: 572 AN XY: 74478

Gnomad4 AFR AF: 0.00149

Gnomad4 AMR AF: 0.0543

Gnomad4 ASJ AF: 0.000288

Gnomad4 EAS AF: 0.00752

Gnomad4 SAS AF: 0.00145

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000191

Gnomad4 OTH AF: 0.00710

Alfa AF: 0.000898 Hom.: 3

Bravo AF: 0.00996

TwinsUK AF: 0.00 AC: 0

ALSPAC AF: 0.000259 AC: 1

ESP6500AA AF: 0.00182 AC: 8

ESP6500EA AF: 0.000465 AC: 4

ExAC AF: 0.00644 AC: 782

Asia WGS AF: 0.00606 AC: 21 AN: 3478

EpiCase AF: 0.000164

EpiControl AF: 0.000178

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jul 06, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.70	T
BayesDel_noAF	Benign	-0.74
CADD	Benign	3.3
DANN	Benign	0.46
DEOGEN2	Benign	0.00080	T
Eigen	Benign	-0.98
Eigen_PC	Benign	-0.97
FATHMM_MKL	Benign	0.047	N
LIST_S2	Benign	0.45	T
MetaRNN	Benign	0.0073	T
MetaSVM	Benign	-0.91	T
MutationAssessor	Benign	0.57	N
PrimateAI	Benign	0.33	T
PROVEAN	Benign	-0.11	N
REVEL	Benign	0.044
Sift	Uncertain	0.016	D
Sift4G	Uncertain	0.0080	D
Polyphen		0.026	B
Vest4		0.056
MVP		0.25
MPC		0.11
ClinPred		0.0013	T
GERP RS		1.7
Varity_R		0.084
gMVP		0.22

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: rs2233997; hg19: chr7-141478305; COSMIC: COSV56093650;