8-143642893-C-T

Position:

• chr8-143642893-C-T

Variant summary

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

The NM_001261843.2(ZNF623):​c.-96+6748C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.425 in 151,918 control chromosomes in the GnomAD database, including 14,654 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 0.43 (14654 hom., cov: 31)
• Consequence: ZNF623 NM_001261843.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.694

Genes affected

ZNF623 (HGNC:29084): (zinc finger protein 623) 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 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=-0.68).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.784 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZNF623	NM_001261843.2	c.-96+6748C>T		intron_variant		ENST00000526926.6	NP_001248772.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZNF623	ENST00000526926.6	c.-96+6748C>T		intron_variant		2	NM_001261843.2	ENSP00000435232.1
ZNF623	ENST00000458270.2	c.-96+6478C>T		intron_variant		1		ENSP00000411139.2

Frequencies

GnomAD3 genomes AF: 0.425 AC: 64563 AN: 151800 Hom.: 14651 Cov.: 31

Gnomad AFR AF: 0.513

Gnomad AMI AF: 0.404

Gnomad AMR AF: 0.445

Gnomad ASJ AF: 0.385

Gnomad EAS AF: 0.805

Gnomad SAS AF: 0.583

Gnomad FIN AF: 0.371

Gnomad MID AF: 0.459

Gnomad NFE AF: 0.338

Gnomad OTH AF: 0.451

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

GnomAD4 genome AF: 0.425 AC: 64607 AN: 151918 Hom.: 14654 Cov.: 31 AF XY: 0.433 AC XY: 32129 AN XY: 74232

Gnomad4 AFR AF: 0.512

Gnomad4 AMR AF: 0.445

Gnomad4 ASJ AF: 0.385

Gnomad4 EAS AF: 0.805

Gnomad4 SAS AF: 0.583

Gnomad4 FIN AF: 0.371

Gnomad4 NFE AF: 0.338

Gnomad4 OTH AF: 0.454

Alfa AF: 0.359 Hom.: 16211

Bravo AF: 0.440

Asia WGS AF: 0.697 AC: 2425 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.68
CADD	Benign	2.4
DANN	Benign	0.89

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs4873815; hg19: chr8-144725063;