Genetic Variant NM_016944.2:c.20T>C (chr7-141778508-T-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

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. 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 0.42 ( 14547 hom., cov: 32)

Exomes 𝑓: 0.48 ( 172644 hom. )

Consequence

TAS2R4
NM_016944.2 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.959

Publications

45 publications found

Variant links:

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]

TAS2R4 links:

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

SSBP1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
TAS2R4	NM_016944.2 link	c.20T>C	p.Phe7Ser	missense_variant	Exon 1 of 1	ENST00000247881.4	NP_058640.1	Q9NYW5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TAS2R4	ENST00000247881.4 link	c.20T>C	p.Phe7Ser	missense_variant	Exon 1 of 1	6	NM_016944.2	ENSP00000247881.3		Q9NYW5
SSBP1	ENST00000465582.5 link	c.*31-9215T>C		intron_variant	Intron 7 of 7	5		ENSP00000420485.1		Q04837

Frequencies

GnomAD3 genomes

AF:

0.422

AC:

64080

AN:

151988

Hom.:

14540

Cov.:

show subpopulations

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

GnomAD2 exomes

AF:

0.479

AC:

119886

AN:

250364

AF XY:

0.482

show subpopulations

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 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.:

AF XY:

0.484

AC XY:

351725

AN XY:

725986

show subpopulations

African (AFR)

AF:

0.220

AC:

7356

AN:

33366

American (AMR)

AF:

0.496

AC:

22128

AN:

44592

Ashkenazi Jewish (ASJ)

AF:

0.453

AC:

11804

AN:

26044

East Asian (EAS)

AF:

0.675

AC:

26774

AN:

39694

South Asian (SAS)

AF:

0.453

AC:

39007

AN:

86056

European-Finnish (FIN)

AF:

0.462

AC:

24653

AN:

53324

Middle Eastern (MID)

AF:

0.476

AC:

2672

AN:

5610

European-Non Finnish (NFE)

AF:

0.488

AC:

542011

AN:

1110588

Other (OTH)

AF:

0.485

AC:

29206

AN:

60278

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.472

Heterozygous variant carriers

17507

35014

52521

70028

87535

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

15918

31836

47754

63672

79590

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.422

AC:

64117

AN:

152108

Hom.:

14547

Cov.:

AF XY:

0.424

AC XY:

31537

AN XY:

74352

show subpopulations

African (AFR)

AF:

0.233

AC:

9672

AN:

41492

American (AMR)

AF:

0.491

AC:

7512

AN:

15288

Ashkenazi Jewish (ASJ)

AF:

0.467

AC:

1621

AN:

3472

East Asian (EAS)

AF:

0.686

AC:

3551

AN:

5174

South Asian (SAS)

AF:

0.441

AC:

2127

AN:

4824

European-Finnish (FIN)

AF:

0.462

AC:

4878

AN:

10568

Middle Eastern (MID)

AF:

0.500

AC:

147

AN:

294

European-Non Finnish (NFE)

AF:

0.492

AC:

33429

AN:

67974

Other (OTH)

AF:

0.455

AC:

960

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1822

3645

5467

7290

9112

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

610

1220

1830

2440

3050

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.469

Hom.:

38400

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

BayesDel_noAF

Benign

-0.75

CADD

Benign

5.8

(source)

DANN

Benign

0.77

DEOGEN2

Benign

0.0017

Eigen

Benign

-1.2

Eigen_PC

Benign

-1.2

FATHMM_MKL

Benign

0.14

LIST_S2

Benign

0.24

MetaRNN

Benign

0.0000061

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.4

PhyloP100

0.96

PrimateAI

Benign

0.31

PROVEAN

Benign

-0.75

REVEL

Benign

0.032

Sift

Benign

0.14

Sift4G

Uncertain

0.042

Polyphen

0.0010

Vest4

0.050

MPC

0.14

ClinPred

0.010

GERP RS

1.6

Varity_R

0.12

gMVP

0.18

Mutation Taster

=99/1

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over