rs201300

Variant names:

• chr6-21033734-T-C
• rs201300
• NM_017774.3:c.1056-31314T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_017774.3(CDKAL1):​c.1056-31314T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.366 in 152,058 control chromosomes in the GnomAD database, including 10,395 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 (10395 hom., cov: 32)
• Consequence: CDKAL1 NM_017774.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.164
• Publications: 7 publications found

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

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.393 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CDKAL1	NM_017774.3	c.1056-31314T>C		intron_variant	Intron 11 of 15	ENST00000274695.8	NP_060244.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CDKAL1	ENST00000274695.8	c.1056-31314T>C		intron_variant	Intron 11 of 15	1	NM_017774.3	ENSP00000274695.4
CDKAL1	ENST00000378610.1	c.1056-31314T>C		intron_variant	Intron 9 of 13	2		ENSP00000367873.1

Frequencies

GnomAD3 genomes AF: 0.366 AC: 55595 AN: 151940 Hom.: 10385 Cov.: 32

Gnomad AFR AF: 0.346

Gnomad AMI AF: 0.387

Gnomad AMR AF: 0.307

Gnomad ASJ AF: 0.424

Gnomad EAS AF: 0.230

Gnomad SAS AF: 0.406

Gnomad FIN AF: 0.376

Gnomad MID AF: 0.449

Gnomad NFE AF: 0.394

Gnomad OTH AF: 0.364

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

GnomAD4 genome AF: 0.366 AC: 55619 AN: 152058 Hom.: 10395 Cov.: 32 AF XY: 0.365 AC XY: 27121 AN XY: 74332

African (AFR) AF: 0.346 AC: 14348 AN: 41478

American (AMR) AF: 0.307 AC: 4677 AN: 15256

Ashkenazi Jewish (ASJ) AF: 0.424 AC: 1470 AN: 3466

East Asian (EAS) AF: 0.230 AC: 1189 AN: 5172

South Asian (SAS) AF: 0.408 AC: 1968 AN: 4822

European-Finnish (FIN) AF: 0.376 AC: 3976 AN: 10576

Middle Eastern (MID) AF: 0.446 AC: 131 AN: 294

European-Non Finnish (NFE) AF: 0.393 AC: 26744 AN: 67974

Other (OTH) AF: 0.362 AC: 763 AN: 2108

Alfa AF: 0.386 Hom.: 19925

Bravo AF: 0.359

Asia WGS AF: 0.308 AC: 1073 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	3.5
DANN	Benign	0.56
PhyloP100		-0.16
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: rs201300; hg19: chr6-21033965;