chr8-76699390-A-G

Position:

• chr8-76699390-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_024721.5(ZFHX4):​c.-46-4653A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.321 in 151,890 control chromosomes in the GnomAD database, including 11,614 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 0.32 (11614 hom., cov: 32)
• Consequence: ZFHX4 NM_024721.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.11

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.662 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZFHX4	NM_024721.5	c.-46-4653A>G		intron_variant		ENST00000651372.2	NP_078997.4
ZFHX4	NM_001410934.1	c.-46-4653A>G		intron_variant			NP_001397863.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZFHX4	ENST00000651372.2	c.-46-4653A>G		intron_variant			NM_024721.5	ENSP00000498627.1

Frequencies

GnomAD3 genomes AF: 0.320 AC: 48615 AN: 151772 Hom.: 11574 Cov.: 32

Gnomad AFR AF: 0.668

Gnomad AMI AF: 0.0791

Gnomad AMR AF: 0.226

Gnomad ASJ AF: 0.130

Gnomad EAS AF: 0.451

Gnomad SAS AF: 0.221

Gnomad FIN AF: 0.199

Gnomad MID AF: 0.215

Gnomad NFE AF: 0.161

Gnomad OTH AF: 0.272

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

GnomAD4 genome AF: 0.321 AC: 48704 AN: 151890 Hom.: 11614 Cov.: 32 AF XY: 0.318 AC XY: 23625 AN XY: 74246

Gnomad4 AFR AF: 0.668

Gnomad4 AMR AF: 0.225

Gnomad4 ASJ AF: 0.130

Gnomad4 EAS AF: 0.451

Gnomad4 SAS AF: 0.221

Gnomad4 FIN AF: 0.199

Gnomad4 NFE AF: 0.162

Gnomad4 OTH AF: 0.270

Alfa AF: 0.172 Hom.: 2796

Bravo AF: 0.338

Asia WGS AF: 0.317 AC: 1102 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	7.8
DANN	Benign	0.46

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

Publications

LitVar

Other links and lift over

dbSNP: rs4735738; hg19: chr8-77611625;