rs1233710

Positions:

• chr6-28247668-C-T

Variant summary

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

The NM_019110.5(ZKSCAN4):​c.654+399G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.127 in 152,190 control chromosomes in the GnomAD database, including 1,961 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 0.13 (1961 hom., cov: 32)
• Consequence: ZKSCAN4 NM_019110.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0900

Genes affected

ZKSCAN4 (HGNC:13854): (zinc finger with KRAB and SCAN domains 4) Enables identical protein binding activity. Predicted to be involved in regulation of transcription by RNA polymerase II. Located in nucleoplasm. [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=-0.85).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.331 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZKSCAN4	NM_019110.5	c.654+399G>A		intron_variant		ENST00000377294.3	NP_061983.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZKSCAN4	ENST00000377294.3	c.654+399G>A		intron_variant		1	NM_019110.5	ENSP00000366509	P1

Frequencies

GnomAD3 genomes AF: 0.127 AC: 19274 AN: 152072 Hom.: 1952 Cov.: 32

Gnomad AFR AF: 0.254

Gnomad AMI AF: 0.0614

Gnomad AMR AF: 0.135

Gnomad ASJ AF: 0.0683

Gnomad EAS AF: 0.345

Gnomad SAS AF: 0.159

Gnomad FIN AF: 0.0444

Gnomad MID AF: 0.130

Gnomad NFE AF: 0.0457

Gnomad OTH AF: 0.112

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

GnomAD4 genome AF: 0.127 AC: 19322 AN: 152190 Hom.: 1961 Cov.: 32 AF XY: 0.129 AC XY: 9570 AN XY: 74418

Gnomad4 AFR AF: 0.254

Gnomad4 AMR AF: 0.135

Gnomad4 ASJ AF: 0.0683

Gnomad4 EAS AF: 0.344

Gnomad4 SAS AF: 0.161

Gnomad4 FIN AF: 0.0444

Gnomad4 NFE AF: 0.0457

Gnomad4 OTH AF: 0.111

Alfa AF: 0.0636 Hom.: 671

Bravo AF: 0.142

Asia WGS AF: 0.170 AC: 590 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	5.2
DANN	Benign	0.24

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: rs1233710; hg19: chr6-28215446; COSMIC: COSV66023515;