rs1233710

Variant names:

• chr6-28247668-C-T
• rs1233710
• NM_019110.5:c.654+399G>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 18 publications found

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

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
ZKSCAN4	NM_019110.5	c.654+399G>A		intron_variant	Intron 3 of 4	ENST00000377294.3	NP_061983.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZKSCAN4	ENST00000377294.3	c.654+399G>A		intron_variant	Intron 3 of 4	1	NM_019110.5	ENSP00000366509.2

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

African (AFR) AF: 0.254 AC: 10551 AN: 41482

American (AMR) AF: 0.135 AC: 2065 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.0683 AC: 237 AN: 3472

East Asian (EAS) AF: 0.344 AC: 1783 AN: 5178

South Asian (SAS) AF: 0.161 AC: 776 AN: 4824

European-Finnish (FIN) AF: 0.0444 AC: 471 AN: 10614

Middle Eastern (MID) AF: 0.143 AC: 42 AN: 294

European-Non Finnish (NFE) AF: 0.0457 AC: 3107 AN: 68016

Other (OTH) AF: 0.111 AC: 234 AN: 2108

Alfa AF: 0.0837 Hom.: 2099

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
PhyloP100		-0.090
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: rs1233710; hg19: chr6-28215446; COSMIC: COSV66023515;