dbSNP rs4908932: ZBTB48:c.-419G>T (chr1-6579787-G-T) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The NM_005341.4(ZBTB48):c.-419G>T variant causes a upstream gene change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.167 in 705,564 control chromosomes in the GnomAD database, including 11,330 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.17 ( 2510 hom., cov: 33)

Exomes 𝑓: 0.17 ( 8820 hom. )

Consequence

ZBTB48
NM_005341.4 upstream_gene

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.372

Publications

14 publications found

Variant links:

Genes affected

ZBTB48 (HGNC:4930): (zinc finger and BTB domain containing 48) Enables double-stranded telomeric DNA binding activity; identical protein binding activity; and transcription cis-regulatory region binding activity. Involved in positive regulation of transcription, DNA-templated and telomere maintenance via telomere lengthening. Located in chromosome, telomeric region. [provided by Alliance of Genome Resources, Apr 2022]

ZBTB48 links:

TAS1R1 (HGNC:14448): (taste 1 receptor member 1) The protein encoded by this gene is a G protein-coupled receptor and is a component of the heterodimeric amino acid taste receptor T1R1+3. The T1R1+3 receptor responds to L-amino acids but not to D-enantiomers or other compounds. Most amino acids that are perceived as sweet activate T1R1+3, and this activation is strictly dependent on an intact T1R1+3 heterodimer. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jun 2010]

TAS1R1 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.85).

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.27 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZBTB48	NM_005341.4 link	c.-419G>T		upstream_gene_variant		ENST00000377674.9	NP_005332.1
TAS1R1	NM_138697.4 link	c.*203G>T		downstream_gene_variant		ENST00000333172.11	NP_619642.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZBTB48	ENST00000377674.9 link	c.-419G>T		upstream_gene_variant		1	NM_005341.4	ENSP00000366902.4
TAS1R1	ENST00000333172.11 link	c.*203G>T		downstream_gene_variant		1	NM_138697.4	ENSP00000331867.6

Frequencies

GnomAD3 genomes

AF:

0.167

AC:

25329

AN:

152126

Hom.:

2505

Cov.:

show subpopulations

Gnomad AFR

AF:

0.112

Gnomad AMI

AF:

0.201

Gnomad AMR

AF:

0.276

Gnomad ASJ

AF:

0.191

Gnomad EAS

AF:

0.00250

Gnomad SAS

AF:

0.0980

Gnomad FIN

AF:

0.220

Gnomad MID

AF:

0.136

Gnomad NFE

AF:

0.182

Gnomad OTH

AF:

0.169

GnomAD4 exome

AF:

0.167

AC:

92180

AN:

553320

Hom.:

8820

Cov.:

AF XY:

0.164

AC XY:

46731

AN XY:

284358

show subpopulations

African (AFR)

AF:

0.109

AC:

1576

AN:

14422

American (AMR)

AF:

0.340

AC:

5704

AN:

16762

Ashkenazi Jewish (ASJ)

AF:

0.174

AC:

2472

AN:

14174

East Asian (EAS)

AF:

0.000393

AC:

AN:

30526

South Asian (SAS)

AF:

0.111

AC:

5009

AN:

44986

European-Finnish (FIN)

AF:

0.207

AC:

5935

AN:

28618

Middle Eastern (MID)

AF:

0.145

AC:

318

AN:

2186

European-Non Finnish (NFE)

AF:

0.178

AC:

66190

AN:

372534

Other (OTH)

AF:

0.171

AC:

4964

AN:

29112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.493

Heterozygous variant carriers

3551

7102

10652

14203

17754

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

1198

2396

3594

4792

5990

<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:

0.166

AC:

25339

AN:

152244

Hom.:

2510

Cov.:

AF XY:

0.168

AC XY:

12475

AN XY:

74446

show subpopulations

African (AFR)

AF:

0.112

AC:

4661

AN:

41552

American (AMR)

AF:

0.277

AC:

4233

AN:

15284

Ashkenazi Jewish (ASJ)

AF:

0.191

AC:

663

AN:

3468

East Asian (EAS)

AF:

0.00270

AC:

AN:

5186

South Asian (SAS)

AF:

0.0971

AC:

469

AN:

4832

European-Finnish (FIN)

AF:

0.220

AC:

2336

AN:

10610

Middle Eastern (MID)

AF:

0.146

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.182

AC:

12384

AN:

67994

Other (OTH)

AF:

0.167

AC:

353

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.495

Heterozygous variant carriers

1066

2133

3199

4266

5332

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

260

520

780

1040

1300

<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:

0.176

Hom.:

4794

Bravo

AF:

0.172

Asia WGS

AF:

0.0710

AC:

250

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.85

CADD

Benign

4.2

(source)

DANN

Benign

0.51

PhyloP100

0.37

PromoterAI

0.10

Neutral

(source)

Mutation Taster

=94/6

polymorphism

(source)

Splicing

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