chr7-100020983-G-A

Variant names:

• chr7-100020983-G-A
• rs6963345
• NM_003439.4:c.-88-2436G>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 9 publications found

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

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
ZKSCAN1	NM_003439.4	c.-88-2436G>A		intron_variant	Intron 1 of 5	ENST00000324306.11	NP_003430.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZKSCAN1	ENST00000324306.11	c.-88-2436G>A		intron_variant	Intron 1 of 5	1	NM_003439.4	ENSP00000323148.6

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

African (AFR) AF: 0.101 AC: 4192 AN: 41424

American (AMR) AF: 0.434 AC: 6619 AN: 15242

Ashkenazi Jewish (ASJ) AF: 0.431 AC: 1495 AN: 3466

East Asian (EAS) AF: 0.417 AC: 2157 AN: 5172

South Asian (SAS) AF: 0.389 AC: 1871 AN: 4810

European-Finnish (FIN) AF: 0.385 AC: 4040 AN: 10484

Middle Eastern (MID) AF: 0.476 AC: 140 AN: 294

European-Non Finnish (NFE) AF: 0.373 AC: 25360 AN: 67960

Other (OTH) AF: 0.351 AC: 742 AN: 2112

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
PhyloP100		0.17
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: rs6963345; hg19: chr7-99618606;