8-76695246-G-A

Variant names:

• chr8-76695246-G-A
• rs10504634
• NM_024721.5:c.-46-8797G>A

Variant summary

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

The NM_024721.5(ZFHX4):​c.-46-8797G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0671 in 152,142 control chromosomes in the GnomAD database, including 374 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 0.067 (374 hom., cov: 31)
• Consequence: ZFHX4 NM_024721.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.06
• Publications: 2 publications found

Genes affected

ZFHX4 (HGNC:30939): (zinc finger homeobox 4) 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 part of chromatin. Predicted to be active in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

ZFHX4-AS1 (HGNC:44165): (ZFHX4 antisense RNA 1)

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 (SAS) allele frequency at 95% confidence interval = 0.102 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZFHX4	NM_024721.5	c.-46-8797G>A		intron_variant	Intron 1 of 10	ENST00000651372.2	NP_078997.4
ZFHX4	NM_001410934.1	c.-46-8797G>A		intron_variant	Intron 1 of 10		NP_001397863.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZFHX4	ENST00000651372.2	c.-46-8797G>A		intron_variant	Intron 1 of 10		NM_024721.5	ENSP00000498627.1

Frequencies

GnomAD3 genomes AF: 0.0671 AC: 10203 AN: 152022 Hom.: 375 Cov.: 31

Gnomad AFR AF: 0.101

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0441

Gnomad ASJ AF: 0.0525

Gnomad EAS AF: 0.0943

Gnomad SAS AF: 0.109

Gnomad FIN AF: 0.0474

Gnomad MID AF: 0.111

Gnomad NFE AF: 0.0515

Gnomad OTH AF: 0.0589

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

GnomAD4 genome AF: 0.0671 AC: 10209 AN: 152142 Hom.: 374 Cov.: 31 AF XY: 0.0681 AC XY: 5062 AN XY: 74386

African (AFR) AF: 0.101 AC: 4182 AN: 41474

American (AMR) AF: 0.0440 AC: 673 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.0525 AC: 182 AN: 3468

East Asian (EAS) AF: 0.0945 AC: 489 AN: 5174

South Asian (SAS) AF: 0.109 AC: 526 AN: 4812

European-Finnish (FIN) AF: 0.0474 AC: 502 AN: 10594

Middle Eastern (MID) AF: 0.109 AC: 32 AN: 294

European-Non Finnish (NFE) AF: 0.0515 AC: 3500 AN: 68008

Other (OTH) AF: 0.0583 AC: 123 AN: 2110

Alfa AF: 0.00955 Hom.: 2

Bravo AF: 0.0676

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.26
DANN	Benign	0.63
PhyloP100		-1.1
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: rs10504634; hg19: chr8-77607481;