rs1040558

Positions:

• chr6-20713475-A-G

Variant summary

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

The NM_017774.3(CDKAL1):​c.372-26044A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.199 in 152,114 control chromosomes in the GnomAD database, including 3,235 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 0.20 (3235 hom., cov: 32)
• Consequence: CDKAL1 NM_017774.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.269

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=-0.98).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.461 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CDKAL1	NM_017774.3	c.372-26044A>G		intron_variant		ENST00000274695.8	NP_060244.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CDKAL1	ENST00000274695.8	c.372-26044A>G		intron_variant		1	NM_017774.3	ENSP00000274695	P1
CDKAL1	ENST00000378610.1	c.372-26044A>G		intron_variant		2		ENSP00000367873	P1

Frequencies

GnomAD3 genomes AF: 0.199 AC: 30214 AN: 151998 Hom.: 3235 Cov.: 32

Gnomad AFR AF: 0.186

Gnomad AMI AF: 0.293

Gnomad AMR AF: 0.201

Gnomad ASJ AF: 0.233

Gnomad EAS AF: 0.477

Gnomad SAS AF: 0.250

Gnomad FIN AF: 0.181

Gnomad MID AF: 0.247

Gnomad NFE AF: 0.181

Gnomad OTH AF: 0.202

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

GnomAD4 genome AF: 0.199 AC: 30218 AN: 152114 Hom.: 3235 Cov.: 32 AF XY: 0.202 AC XY: 15019 AN XY: 74360

Gnomad4 AFR AF: 0.186

Gnomad4 AMR AF: 0.201

Gnomad4 ASJ AF: 0.233

Gnomad4 EAS AF: 0.477

Gnomad4 SAS AF: 0.250

Gnomad4 FIN AF: 0.181

Gnomad4 NFE AF: 0.181

Gnomad4 OTH AF: 0.200

Alfa AF: 0.189 Hom.: 2406

Bravo AF: 0.201

Asia WGS AF: 0.292 AC: 1007 AN: 3464

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	0.62
DANN	Benign	0.77

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: rs1040558; hg19: chr6-20713706;