1-173899817-C-T

Variant names:

• chr1-173899817-C-T
• rs6691053
• NM_001122770.3:c.*13693C>T

Variant summary

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

The NM_001122770.3(ZBTB37):​c.*13693C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.272 in 152,024 control chromosomes in the GnomAD database, including 6,268 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 0.27 (6268 hom., cov: 32)
  • Exomes 𝑓: 0.25 (0 hom.)
• Consequence: ZBTB37 NM_001122770.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.77
• Publications: 12 publications found

Genes affected

ZBTB37 (HGNC:28365): (zinc finger and BTB domain containing 37) Enables sequence-specific double-stranded DNA binding activity. Predicted to be involved in regulation of transcription by RNA polymerase II. Predicted to be part of chromatin. Predicted to be active in nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.387 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZBTB37	NM_001122770.3	c.*13693C>T		3_prime_UTR_variant	Exon 5 of 5	ENST00000367701.10	NP_001116242.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZBTB37	ENST00000367701.10	c.*13693C>T		3_prime_UTR_variant	Exon 5 of 5	1	NM_001122770.3	ENSP00000356674.4

Frequencies

GnomAD3 genomes AF: 0.272 AC: 41330 AN: 151902 Hom.: 6256 Cov.: 32

Gnomad AFR AF: 0.392

Gnomad AMI AF: 0.237

Gnomad AMR AF: 0.236

Gnomad ASJ AF: 0.346

Gnomad EAS AF: 0.372

Gnomad SAS AF: 0.225

Gnomad FIN AF: 0.182

Gnomad MID AF: 0.304

Gnomad NFE AF: 0.213

Gnomad OTH AF: 0.266

GnomAD4 exome AF: 0.250 AC: 1 AN: 4 Hom.: 0 Cov.: 0 AF XY: 0.250 AC XY: 1 AN XY: 4

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.250 AC: 1 AN: 4

Other (OTH) AC: 0 AN: 0

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome AF: 0.272 AC: 41381 AN: 152020 Hom.: 6268 Cov.: 32 AF XY: 0.270 AC XY: 20047 AN XY: 74302

African (AFR) AF: 0.392 AC: 16251 AN: 41436

American (AMR) AF: 0.237 AC: 3614 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.346 AC: 1201 AN: 3470

East Asian (EAS) AF: 0.372 AC: 1923 AN: 5166

South Asian (SAS) AF: 0.225 AC: 1084 AN: 4824

European-Finnish (FIN) AF: 0.182 AC: 1925 AN: 10564

Middle Eastern (MID) AF: 0.320 AC: 94 AN: 294

European-Non Finnish (NFE) AF: 0.213 AC: 14509 AN: 67970

Other (OTH) AF: 0.268 AC: 565 AN: 2112

Alfa AF: 0.216 Hom.: 2520

Bravo AF: 0.283

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.18
DANN	Benign	0.49
PhyloP100		-1.8
Mutation Taster		=100/0	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs6691053; hg19: chr1-173868955;