6-20622522-C-T

Variant names:

• chr6-20622522-C-T
• rs1569660
• NM_017774.3:c.287-26771C>T

Variant summary

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

The NM_017774.3(CDKAL1):​c.287-26771C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.574 in 151,712 control chromosomes in the GnomAD database, including 25,301 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 0.57 (25301 hom., cov: 31)
• Consequence: CDKAL1 NM_017774.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0930
• Publications: 10 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=-0.87).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.798 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CDKAL1	NM_017774.3	c.287-26771C>T		intron_variant	Intron 4 of 15	ENST00000274695.8	NP_060244.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CDKAL1	ENST00000274695.8	c.287-26771C>T		intron_variant	Intron 4 of 15	1	NM_017774.3	ENSP00000274695.4
CDKAL1	ENST00000378610.1	c.287-26771C>T		intron_variant	Intron 2 of 13	2		ENSP00000367873.1

Frequencies

GnomAD3 genomes AF: 0.574 AC: 87084 AN: 151594 Hom.: 25300 Cov.: 31

Gnomad AFR AF: 0.531

Gnomad AMI AF: 0.607

Gnomad AMR AF: 0.609

Gnomad ASJ AF: 0.587

Gnomad EAS AF: 0.819

Gnomad SAS AF: 0.657

Gnomad FIN AF: 0.580

Gnomad MID AF: 0.703

Gnomad NFE AF: 0.565

Gnomad OTH AF: 0.599

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

GnomAD4 genome AF: 0.574 AC: 87132 AN: 151712 Hom.: 25301 Cov.: 31 AF XY: 0.578 AC XY: 42884 AN XY: 74132

African (AFR) AF: 0.531 AC: 21959 AN: 41336

American (AMR) AF: 0.608 AC: 9260 AN: 15226

Ashkenazi Jewish (ASJ) AF: 0.587 AC: 2032 AN: 3464

East Asian (EAS) AF: 0.818 AC: 4230 AN: 5168

South Asian (SAS) AF: 0.656 AC: 3162 AN: 4818

European-Finnish (FIN) AF: 0.580 AC: 6111 AN: 10534

Middle Eastern (MID) AF: 0.694 AC: 204 AN: 294

European-Non Finnish (NFE) AF: 0.565 AC: 38366 AN: 67858

Other (OTH) AF: 0.597 AC: 1257 AN: 2106

Alfa AF: 0.579 Hom.: 39909

Bravo AF: 0.575

Asia WGS AF: 0.672 AC: 2336 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	7.1
DANN	Benign	0.78
PhyloP100		0.093
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: rs1569660; hg19: chr6-20622753;