rs1004172

Positions:

• chr6-20954595-G-A
• chr6-20954595-G-T

Variant summary

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

The NM_017774.3(CDKAL1):​c.743-824G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.177 in 152,056 control chromosomes in the GnomAD database, including 2,763 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 0.18 (2763 hom., cov: 32)
• Consequence: CDKAL1 NM_017774.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.13

Genes affected

CDKAL1 (HGNC:21050): (CDK5 regulatory subunit associated protein 1 like 1) The protein encoded by this gene is a member of the methylthiotransferase family. The function of this gene is not known. Genome-wide association studies have linked single nucleotide polymorphisms in an intron of this gene with susceptibilty to type 2 diabetes. [provided by RefSeq, May 2010]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.25 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CDKAL1	NM_017774.3	c.743-824G>A		intron_variant		ENST00000274695.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CDKAL1	ENST00000274695.8	c.743-824G>A		intron_variant		1	NM_017774.3	P1
CDKAL1	ENST00000378610.1	c.743-824G>A		intron_variant		2		P1

Frequencies

GnomAD3 genomes AF: 0.177 AC: 26939 AN: 151938 Hom.: 2759 Cov.: 32

Gnomad AFR AF: 0.0828

Gnomad AMI AF: 0.157

Gnomad AMR AF: 0.256

Gnomad ASJ AF: 0.151

Gnomad EAS AF: 0.233

Gnomad SAS AF: 0.192

Gnomad FIN AF: 0.144

Gnomad MID AF: 0.253

Gnomad NFE AF: 0.217

Gnomad OTH AF: 0.208

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

GnomAD4 genome AF: 0.177 AC: 26949 AN: 152056 Hom.: 2763 Cov.: 32 AF XY: 0.176 AC XY: 13063 AN XY: 74298

Gnomad4 AFR AF: 0.0827

Gnomad4 AMR AF: 0.257

Gnomad4 ASJ AF: 0.151

Gnomad4 EAS AF: 0.234

Gnomad4 SAS AF: 0.191

Gnomad4 FIN AF: 0.144

Gnomad4 NFE AF: 0.217

Gnomad4 OTH AF: 0.205

Alfa AF: 0.211 Hom.: 5843

Bravo AF: 0.184

Asia WGS AF: 0.178 AC: 620 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.40
DANN	Benign	0.59

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: rs1004172; hg19: chr6-20954826;