1-197172858-G-T

Variant names:

• chr1-197172858-G-T
• rs4520444
• NM_194314.3:c.1986-610C>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.1986-610C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.255 in 151,928 control chromosomes in the GnomAD database, including 5,309 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 0.25 (5309 hom., cov: 32)
• Consequence: ZBTB41 NM_194314.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.184
• Publications: 4 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=-0.93).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.303 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZBTB41	NM_194314.3	c.1986-610C>A		intron_variant	Intron 9 of 10	ENST00000367405.5	NP_919290.2
ZBTB41	NR_135153.2	n.2258-610C>A		intron_variant	Intron 10 of 11
ZBTB41	XM_047419671.1	c.1986-610C>A		intron_variant	Intron 9 of 10		XP_047275627.1
ZBTB41	XM_011509507.4	c.1986-610C>A		intron_variant	Intron 9 of 10		XP_011507809.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZBTB41	ENST00000367405.5	c.1986-610C>A		intron_variant	Intron 9 of 10	1	NM_194314.3	ENSP00000356375.3
ZBTB41	ENST00000467322.1	n.*186-610C>A		intron_variant	Intron 9 of 10	2		ENSP00000502173.1

Frequencies

GnomAD3 genomes AF: 0.255 AC: 38710 AN: 151810 Hom.: 5304 Cov.: 32

Gnomad AFR AF: 0.163

Gnomad AMI AF: 0.487

Gnomad AMR AF: 0.252

Gnomad ASJ AF: 0.305

Gnomad EAS AF: 0.122

Gnomad SAS AF: 0.299

Gnomad FIN AF: 0.297

Gnomad MID AF: 0.318

Gnomad NFE AF: 0.306

Gnomad OTH AF: 0.254

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

GnomAD4 genome AF: 0.255 AC: 38718 AN: 151928 Hom.: 5309 Cov.: 32 AF XY: 0.253 AC XY: 18762 AN XY: 74258

African (AFR) AF: 0.163 AC: 6746 AN: 41468

American (AMR) AF: 0.252 AC: 3841 AN: 15236

Ashkenazi Jewish (ASJ) AF: 0.305 AC: 1057 AN: 3468

East Asian (EAS) AF: 0.121 AC: 629 AN: 5182

South Asian (SAS) AF: 0.298 AC: 1438 AN: 4824

European-Finnish (FIN) AF: 0.297 AC: 3126 AN: 10534

Middle Eastern (MID) AF: 0.318 AC: 93 AN: 292

European-Non Finnish (NFE) AF: 0.306 AC: 20807 AN: 67906

Other (OTH) AF: 0.255 AC: 538 AN: 2108

Alfa AF: 0.298 Hom.: 5032

Bravo AF: 0.248

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	1.0
DANN	Benign	0.36
PhyloP100		0.18
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: rs4520444; hg19: chr1-197141988;