rs4908932

Variant names:

• chr1-6579787-G-T
• rs4908932
• NM_005341.4:c.-419G>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.372
• Publications: 14 publications found

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]

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]

ACMG classification

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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005341.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZBTB48	NM_005341.4	MANE Select	c.-419G>T		upstream_gene	N/A	NP_005332.1
	TAS1R1	NM_138697.4	MANE Select	c.*203G>T		downstream_gene	N/A	NP_619642.2
	ZBTB48	NM_001278647.2		c.-332G>T		upstream_gene	N/A	NP_001265576.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZBTB48	ENST00000377674.9	TSL:1 MANE Select	c.-419G>T		upstream_gene	N/A	ENSP00000366902.4
	TAS1R1	ENST00000333172.11	TSL:1 MANE Select	c.*203G>T		downstream_gene	N/A	ENSP00000331867.6
	ZBTB48	ENST00000902999.1		c.-419G>T		upstream_gene	N/A	ENSP00000573058.1

Frequencies

GnomAD3 genomes AF: 0.167 AC: 25329 AN: 152126 Hom.: 2505 Cov.: 33

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.: 7 AF XY: 0.164 AC XY: 46731 AN XY: 284358

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: 12 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

GnomAD4 genome AF: 0.166 AC: 25339 AN: 152244 Hom.: 2510 Cov.: 33 AF XY: 0.168 AC XY: 12475 AN XY: 74446

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: 14 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: 43 AN: 294

European-Non Finnish (NFE) AF: 0.182 AC: 12384 AN: 67994

Other (OTH) AF: 0.167 AC: 353 AN: 2114

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	4.2
DANN	Benign	0.51
PhyloP100		0.37
PromoterAI		0.10	Neutral
Mutation Taster		=94/6	polymorphism

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs4908932; hg19: chr1-6639847;