6-20686765-C-A

Variant names:

• chr6-20686765-C-A
• rs9368222
• NM_017774.3:c.371+37388C>A

Variant summary

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

The NM_017774.3(CDKAL1):​c.371+37388C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.254 in 151,852 control chromosomes in the GnomAD database, including 5,125 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 0.25 (5125 hom., cov: 31)
• Consequence: CDKAL1 NM_017774.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.457
• Publications: 65 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=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.362 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CDKAL1	NM_017774.3	c.371+37388C>A		intron_variant	Intron 5 of 15	ENST00000274695.8	NP_060244.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CDKAL1	ENST00000274695.8	c.371+37388C>A		intron_variant	Intron 5 of 15	1	NM_017774.3	ENSP00000274695.4
CDKAL1	ENST00000378610.1	c.371+37388C>A		intron_variant	Intron 3 of 13	2		ENSP00000367873.1

Frequencies

GnomAD3 genomes AF: 0.254 AC: 38566 AN: 151732 Hom.: 5121 Cov.: 31

Gnomad AFR AF: 0.190

Gnomad AMI AF: 0.363

Gnomad AMR AF: 0.238

Gnomad ASJ AF: 0.281

Gnomad EAS AF: 0.377

Gnomad SAS AF: 0.262

Gnomad FIN AF: 0.349

Gnomad MID AF: 0.272

Gnomad NFE AF: 0.269

Gnomad OTH AF: 0.244

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

GnomAD4 genome AF: 0.254 AC: 38568 AN: 151852 Hom.: 5125 Cov.: 31 AF XY: 0.261 AC XY: 19328 AN XY: 74192

African (AFR) AF: 0.190 AC: 7866 AN: 41408

American (AMR) AF: 0.238 AC: 3638 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.281 AC: 973 AN: 3464

East Asian (EAS) AF: 0.376 AC: 1937 AN: 5146

South Asian (SAS) AF: 0.262 AC: 1265 AN: 4822

European-Finnish (FIN) AF: 0.349 AC: 3660 AN: 10498

Middle Eastern (MID) AF: 0.269 AC: 79 AN: 294

European-Non Finnish (NFE) AF: 0.269 AC: 18305 AN: 67942

Other (OTH) AF: 0.245 AC: 516 AN: 2106

Alfa AF: 0.256 Hom.: 13803

Bravo AF: 0.242

Asia WGS AF: 0.294 AC: 1021 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.36
DANN	Benign	0.50
PhyloP100		-0.46
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: rs9368222; hg19: chr6-20686996;