rs6656448

Variant names:

• chr1-197174148-C-T
• rs6656448
• NM_194314.3:c.1985+862G>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.1985+862G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.775 in 151,594 control chromosomes in the GnomAD database, including 48,915 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 0.78 (48915 hom., cov: 32)
• Consequence: ZBTB41 NM_194314.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.03
• Publications: 3 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=-0.83).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.976 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZBTB41	NM_194314.3	c.1985+862G>A		intron_variant	Intron 9 of 10	ENST00000367405.5	NP_919290.2
ZBTB41	NR_135153.2	n.2257+862G>A		intron_variant	Intron 10 of 11
ZBTB41	XM_047419671.1	c.1985+862G>A		intron_variant	Intron 9 of 10		XP_047275627.1
ZBTB41	XM_011509507.4	c.1985+862G>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.1985+862G>A		intron_variant	Intron 9 of 10	1	NM_194314.3	ENSP00000356375.3
ZBTB41	ENST00000467322.1	n.*185+862G>A		intron_variant	Intron 9 of 10	2		ENSP00000502173.1

Frequencies

GnomAD3 genomes AF: 0.775 AC: 117457 AN: 151478 Hom.: 48892 Cov.: 32

Gnomad AFR AF: 0.437

Gnomad AMI AF: 0.955

Gnomad AMR AF: 0.869

Gnomad ASJ AF: 0.901

Gnomad EAS AF: 0.999

Gnomad SAS AF: 0.899

Gnomad FIN AF: 0.904

Gnomad MID AF: 0.892

Gnomad NFE AF: 0.904

Gnomad OTH AF: 0.807

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

GnomAD4 genome AF: 0.775 AC: 117527 AN: 151594 Hom.: 48915 Cov.: 32 AF XY: 0.779 AC XY: 57726 AN XY: 74060

African (AFR) AF: 0.437 AC: 18021 AN: 41258

American (AMR) AF: 0.869 AC: 13211 AN: 15204

Ashkenazi Jewish (ASJ) AF: 0.901 AC: 3122 AN: 3464

East Asian (EAS) AF: 0.999 AC: 5136 AN: 5140

South Asian (SAS) AF: 0.900 AC: 4334 AN: 4818

European-Finnish (FIN) AF: 0.904 AC: 9545 AN: 10560

Middle Eastern (MID) AF: 0.905 AC: 266 AN: 294

European-Non Finnish (NFE) AF: 0.904 AC: 61321 AN: 67842

Other (OTH) AF: 0.809 AC: 1704 AN: 2106

Alfa AF: 0.813 Hom.: 6715

Bravo AF: 0.758

Asia WGS AF: 0.919 AC: 3194 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	0.29
DANN	Benign	0.23
PhyloP100		-2.0
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: rs6656448; hg19: chr1-197143278;