rs6136363

Positions:

• chr20-18406000-A-G

Variant summary

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

The NM_001367614.1(DZANK1):​c.1507+6646T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.368 in 152,142 control chromosomes in the GnomAD database, including 11,193 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 0.37 (11193 hom., cov: 33)
• Consequence: DZANK1 NM_001367614.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.225

Genes affected

DZANK1 (HGNC:15858): (double zinc ribbon and ankyrin repeat domains 1) This gene contains two ankyrin repeat-encoding regions. Ankyrin repeats are tandemly repeated modules of about 33 amino acids described as L-shaped structures consisting of a beta-hairpin and two alpha-helices. Ankyrin repeats occur in a large number of functionally diverse proteins, mainly from eukaryotes, and are known to function as protein-protein interaction domains. [provided by RefSeq, Dec 2018]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.448 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DZANK1	NM_001367614.1	c.1507+6646T>C		intron_variant		ENST00000699568.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DZANK1	ENST00000699568.1	c.1507+6646T>C		intron_variant			NM_001367614.1	P2

Frequencies

GnomAD3 genomes AF: 0.368 AC: 56018 AN: 152024 Hom.: 11182 Cov.: 33

Gnomad AFR AF: 0.244

Gnomad AMI AF: 0.598

Gnomad AMR AF: 0.327

Gnomad ASJ AF: 0.414

Gnomad EAS AF: 0.129

Gnomad SAS AF: 0.403

Gnomad FIN AF: 0.439

Gnomad MID AF: 0.449

Gnomad NFE AF: 0.452

Gnomad OTH AF: 0.388

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

GnomAD4 genome AF: 0.368 AC: 56036 AN: 152142 Hom.: 11193 Cov.: 33 AF XY: 0.366 AC XY: 27199 AN XY: 74364

Gnomad4 AFR AF: 0.244

Gnomad4 AMR AF: 0.327

Gnomad4 ASJ AF: 0.414

Gnomad4 EAS AF: 0.128

Gnomad4 SAS AF: 0.403

Gnomad4 FIN AF: 0.439

Gnomad4 NFE AF: 0.452

Gnomad4 OTH AF: 0.386

Alfa AF: 0.428 Hom.: 13371

Bravo AF: 0.349

Asia WGS AF: 0.267 AC: 933 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	5.8
DANN	Benign	0.65

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: rs6136363; hg19: chr20-18386644;