rs12137359

Variant names:

• chr1-197160851-C-T
• rs12137359
• NM_194314.3:c.2075-837G>A

Variant summary

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

The NM_194314.3(ZBTB41):​c.2075-837G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.176 in 151,934 control chromosomes in the GnomAD database, including 3,856 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 0.18 (3856 hom., cov: 32)
• Consequence: ZBTB41 NM_194314.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0990
• Publications: 5 publications found

Genes affected

ZBTB41 (HGNC:24819): (zinc finger and BTB domain containing 41) Predicted to enable DNA-binding transcription factor activity, RNA polymerase II-specific and RNA polymerase II cis-regulatory region sequence-specific DNA binding activity. Predicted to be involved in regulation of transcription by RNA polymerase II. Predicted to be located in nucleus. [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=-0.94).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.676 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZBTB41	NM_194314.3	c.2075-837G>A		intron_variant	Intron 10 of 10	ENST00000367405.5	NP_919290.2
ZBTB41	NR_135153.2	n.2347-837G>A		intron_variant	Intron 11 of 11
ZBTB41	XM_047419671.1	c.2075-837G>A		intron_variant	Intron 10 of 10		XP_047275627.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZBTB41	ENST00000367405.5	c.2075-837G>A		intron_variant	Intron 10 of 10	1	NM_194314.3	ENSP00000356375.3
ZBTB41	ENST00000467322.1	n.*275-837G>A		intron_variant	Intron 10 of 10	2		ENSP00000502173.1

Frequencies

GnomAD3 genomes AF: 0.176 AC: 26738 AN: 151816 Hom.: 3846 Cov.: 32

Gnomad AFR AF: 0.0443

Gnomad AMI AF: 0.0647

Gnomad AMR AF: 0.334

Gnomad ASJ AF: 0.191

Gnomad EAS AF: 0.695

Gnomad SAS AF: 0.307

Gnomad FIN AF: 0.249

Gnomad MID AF: 0.114

Gnomad NFE AF: 0.161

Gnomad OTH AF: 0.194

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.176 AC: 26755 AN: 151934 Hom.: 3856 Cov.: 32 AF XY: 0.189 AC XY: 14019 AN XY: 74260

African (AFR) AF: 0.0442 AC: 1834 AN: 41456

American (AMR) AF: 0.335 AC: 5108 AN: 15236

Ashkenazi Jewish (ASJ) AF: 0.191 AC: 663 AN: 3472

East Asian (EAS) AF: 0.695 AC: 3595 AN: 5170

South Asian (SAS) AF: 0.306 AC: 1472 AN: 4808

European-Finnish (FIN) AF: 0.249 AC: 2620 AN: 10530

Middle Eastern (MID) AF: 0.119 AC: 35 AN: 294

European-Non Finnish (NFE) AF: 0.161 AC: 10954 AN: 67946

Other (OTH) AF: 0.197 AC: 415 AN: 2110

Alfa AF: 0.167 Hom.: 1257

Bravo AF: 0.180

Asia WGS AF: 0.483 AC: 1678 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	1.0
DANN	Benign	0.69
PhyloP100		-0.099
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs12137359; hg19: chr1-197129981;