rs6963345

Positions:

• chr7-100020983-G-A
• chr7-100020983-G-C

Variant summary

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

The NM_003439.4(ZKSCAN1):​c.-88-2436G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.309 in 151,874 control chromosomes in the GnomAD database, including 8,743 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 0.31 (8743 hom., cov: 32)
• Consequence: ZKSCAN1 NM_003439.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.172

Genes affected

ZKSCAN1 (HGNC:13101): (zinc finger with KRAB and SCAN domains 1) This gene encodes a member of the Kruppel C2H2-type zinc-finger family of proteins. This encoded protein may function as a transcription factor that regulates the expression of GABA type-A receptors in the brain. Transcripts from this gene have been shown to form stable and abundant circular RNAs. Elevated expression of this gene has been observed in gastric cancer and the encoded protein may stimulate migration and invasion of human gastric cancer cells. [provided by RefSeq, Oct 2016]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.98).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.426 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZKSCAN1	NM_003439.4	c.-88-2436G>A		intron_variant		ENST00000324306.11	NP_003430.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZKSCAN1	ENST00000324306.11	c.-88-2436G>A		intron_variant		1	NM_003439.4	ENSP00000323148	P1

Frequencies

GnomAD3 genomes AF: 0.310 AC: 47009 AN: 151758 Hom.: 8746 Cov.: 32

Gnomad AFR AF: 0.101

Gnomad AMI AF: 0.425

Gnomad AMR AF: 0.434

Gnomad ASJ AF: 0.431

Gnomad EAS AF: 0.418

Gnomad SAS AF: 0.388

Gnomad FIN AF: 0.385

Gnomad MID AF: 0.484

Gnomad NFE AF: 0.373

Gnomad OTH AF: 0.351

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

GnomAD4 genome AF: 0.309 AC: 47003 AN: 151874 Hom.: 8743 Cov.: 32 AF XY: 0.316 AC XY: 23468 AN XY: 74162

Gnomad4 AFR AF: 0.101

Gnomad4 AMR AF: 0.434

Gnomad4 ASJ AF: 0.431

Gnomad4 EAS AF: 0.417

Gnomad4 SAS AF: 0.389

Gnomad4 FIN AF: 0.385

Gnomad4 NFE AF: 0.373

Gnomad4 OTH AF: 0.351

Alfa AF: 0.232 Hom.: 748

Bravo AF: 0.306

Asia WGS AF: 0.359 AC: 1246 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	1.5
DANN	Benign	0.56

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: rs6963345; hg19: chr7-99618606;