rs2248913

Positions:

• chr8-76842916-T-C

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_024721.5(ZFHX4):​c.3511+145T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.212 in 507,072 control chromosomes in the GnomAD database, including 13,783 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 0.19 (3434 hom., cov: 32)
  • Exomes 𝑓: 0.22 (10349 hom.)
• Consequence: ZFHX4 NM_024721.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.424

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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.44).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.259 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ZFHX4	NM_024721.5	c.3511+145T>C		intron_variant		ENST00000651372.2
ZFHX4	NM_001410934.1	c.3433+145T>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ZFHX4	ENST00000651372.2	c.3511+145T>C		intron_variant			NM_024721.5	P4

Frequencies

GnomAD3 genomes AF: 0.192 AC: 29215 AN: 152006 Hom.: 3434 Cov.: 32

Gnomad AFR AF: 0.0758

Gnomad AMI AF: 0.282

Gnomad AMR AF: 0.153

Gnomad ASJ AF: 0.202

Gnomad EAS AF: 0.0403

Gnomad SAS AF: 0.261

Gnomad FIN AF: 0.288

Gnomad MID AF: 0.139

Gnomad NFE AF: 0.262

Gnomad OTH AF: 0.185

GnomAD4 exome AF: 0.221 AC: 78271 AN: 354948 Hom.: 10349 AF XY: 0.222 AC XY: 40949 AN XY: 184164

Gnomad4 AFR exome AF: 0.0769

Gnomad4 AMR exome AF: 0.122

Gnomad4 ASJ exome AF: 0.194

Gnomad4 EAS exome AF: 0.0344

Gnomad4 SAS exome AF: 0.234

Gnomad4 FIN exome AF: 0.261

Gnomad4 NFE exome AF: 0.253

Gnomad4 OTH exome AF: 0.215

GnomAD4 genome AF: 0.192 AC: 29220 AN: 152124 Hom.: 3434 Cov.: 32 AF XY: 0.193 AC XY: 14357 AN XY: 74378

Gnomad4 AFR AF: 0.0756

Gnomad4 AMR AF: 0.153

Gnomad4 ASJ AF: 0.202

Gnomad4 EAS AF: 0.0402

Gnomad4 SAS AF: 0.260

Gnomad4 FIN AF: 0.288

Gnomad4 NFE AF: 0.262

Gnomad4 OTH AF: 0.188

Alfa AF: 0.224 Hom.: 1335

Bravo AF: 0.174

Asia WGS AF: 0.153 AC: 534 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.44
CADD	Benign	15
DANN	Benign	0.86

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: rs2248913; hg19: chr8-77755152; COSMIC: COSV50864650;