rs201351

Variant names:

• chr6-20985899-C-T
• rs201351
• NM_017774.3:c.910-14328C>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.910-14328C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.088 in 151,490 control chromosomes in the GnomAD database, including 716 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 0.088 (716 hom., cov: 32)
• Consequence: CDKAL1 NM_017774.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.194
• Publications: 5 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 (NFE) allele frequency at 95% confidence interval = 0.11 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CDKAL1	NM_017774.3	c.910-14328C>T		intron_variant	Intron 10 of 15	ENST00000274695.8	NP_060244.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CDKAL1	ENST00000274695.8	c.910-14328C>T		intron_variant	Intron 10 of 15	1	NM_017774.3	ENSP00000274695.4
CDKAL1	ENST00000378610.1	c.910-14328C>T		intron_variant	Intron 8 of 13	2		ENSP00000367873.1

Frequencies

GnomAD3 genomes AF: 0.0880 AC: 13319 AN: 151400 Hom.: 715 Cov.: 32

Gnomad AFR AF: 0.0565

Gnomad AMI AF: 0.128

Gnomad AMR AF: 0.0852

Gnomad ASJ AF: 0.149

Gnomad EAS AF: 0.00135

Gnomad SAS AF: 0.0415

Gnomad FIN AF: 0.0962

Gnomad MID AF: 0.165

Gnomad NFE AF: 0.112

Gnomad OTH AF: 0.0938

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

GnomAD4 genome AF: 0.0880 AC: 13327 AN: 151490 Hom.: 716 Cov.: 32 AF XY: 0.0858 AC XY: 6345 AN XY: 73986

African (AFR) AF: 0.0565 AC: 2341 AN: 41434

American (AMR) AF: 0.0850 AC: 1292 AN: 15202

Ashkenazi Jewish (ASJ) AF: 0.149 AC: 515 AN: 3468

East Asian (EAS) AF: 0.00135 AC: 7 AN: 5178

South Asian (SAS) AF: 0.0426 AC: 205 AN: 4810

European-Finnish (FIN) AF: 0.0962 AC: 985 AN: 10242

Middle Eastern (MID) AF: 0.168 AC: 48 AN: 286

European-Non Finnish (NFE) AF: 0.112 AC: 7622 AN: 67860

Other (OTH) AF: 0.0929 AC: 195 AN: 2098

Alfa AF: 0.0960 Hom.: 98

Bravo AF: 0.0873

Asia WGS AF: 0.0270 AC: 94 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	0.76
DANN	Benign	0.29
PhyloP100		-0.19
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: rs201351; hg19: chr6-20986130;