rs16846526

Variant names:

• chr1-173887099-G-A
• rs16846526
• NM_001122770.3:c.*975G>A

Variant summary

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

The NM_001122770.3(ZBTB37):​c.*975G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.1 in 152,164 control chromosomes in the GnomAD database, including 962 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 0.10 (962 hom., cov: 32)
  • Failed GnomAD Quality Control
• Consequence: ZBTB37 NM_001122770.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.89
• Publications: 2 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=-0.47).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.297 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZBTB37	NM_001122770.3	c.*975G>A		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.*975G>A		3_prime_UTR_variant	Exon 5 of 5	1	NM_001122770.3	ENSP00000356674.4
ZBTB37	ENST00000695459.1	c.*975G>A		3_prime_UTR_variant	Exon 5 of 5			ENSP00000511931.1

Frequencies

GnomAD3 genomes AF: 0.100 AC: 15261 AN: 152046 Hom.: 963 Cov.: 32

Gnomad AFR AF: 0.0640

Gnomad AMI AF: 0.101

Gnomad AMR AF: 0.0874

Gnomad ASJ AF: 0.157

Gnomad EAS AF: 0.309

Gnomad SAS AF: 0.145

Gnomad FIN AF: 0.106

Gnomad MID AF: 0.108

Gnomad NFE AF: 0.102

Gnomad OTH AF: 0.111

GnomAD4 exome Data not reliable, filtered out with message: AC0 AC: 0 AN: 0 Hom.: 0 Cov.: 0 AC XY: 0 AN XY: 0

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) AC: 0 AN: 0

Other (OTH) AC: 0 AN: 0

GnomAD4 genome AF: 0.100 AC: 15263 AN: 152164 Hom.: 962 Cov.: 32 AF XY: 0.102 AC XY: 7616 AN XY: 74388

African (AFR) AF: 0.0639 AC: 2654 AN: 41532

American (AMR) AF: 0.0873 AC: 1335 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.157 AC: 546 AN: 3468

East Asian (EAS) AF: 0.309 AC: 1596 AN: 5162

South Asian (SAS) AF: 0.145 AC: 700 AN: 4824

European-Finnish (FIN) AF: 0.106 AC: 1122 AN: 10576

Middle Eastern (MID) AF: 0.116 AC: 34 AN: 294

European-Non Finnish (NFE) AF: 0.102 AC: 6947 AN: 67994

Other (OTH) AF: 0.112 AC: 237 AN: 2112

Alfa AF: 0.0937 Hom.: 159

Bravo AF: 0.0971

Asia WGS AF: 0.224 AC: 778 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.47
CADD	Benign	18
DANN	Benign	0.78
PhyloP100		2.9
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: rs16846526; hg19: chr1-173856237;