6-20717024-T-C

Variant names:

• chr6-20717024-T-C
• rs9465871
• NM_017774.3:c.372-22495T>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.372-22495T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.303 in 151,650 control chromosomes in the GnomAD database, including 8,803 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 0.30 (8803 hom., cov: 31)
• Consequence: CDKAL1 NM_017774.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.71
• Publications: 84 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=-0.93).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.528 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_017774.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CDKAL1	NM_017774.3	MANE Select	c.372-22495T>C		intron	N/A	NP_060244.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CDKAL1	ENST00000274695.8	TSL:1 MANE Select	c.372-22495T>C		intron	N/A	ENSP00000274695.4
	CDKAL1	ENST00000378610.1	TSL:2	c.372-22495T>C		intron	N/A	ENSP00000367873.1

Frequencies

GnomAD3 genomes AF: 0.302 AC: 45808 AN: 151530 Hom.: 8778 Cov.: 31

Gnomad AFR AF: 0.534

Gnomad AMI AF: 0.292

Gnomad AMR AF: 0.253

Gnomad ASJ AF: 0.263

Gnomad EAS AF: 0.476

Gnomad SAS AF: 0.257

Gnomad FIN AF: 0.182

Gnomad MID AF: 0.285

Gnomad NFE AF: 0.184

Gnomad OTH AF: 0.288

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

GnomAD4 genome AF: 0.303 AC: 45875 AN: 151650 Hom.: 8803 Cov.: 31 AF XY: 0.302 AC XY: 22362 AN XY: 74048

African (AFR) AF: 0.534 AC: 22065 AN: 41318

American (AMR) AF: 0.253 AC: 3852 AN: 15226

Ashkenazi Jewish (ASJ) AF: 0.263 AC: 911 AN: 3470

East Asian (EAS) AF: 0.475 AC: 2428 AN: 5108

South Asian (SAS) AF: 0.257 AC: 1232 AN: 4786

European-Finnish (FIN) AF: 0.182 AC: 1919 AN: 10516

Middle Eastern (MID) AF: 0.286 AC: 84 AN: 294

European-Non Finnish (NFE) AF: 0.184 AC: 12515 AN: 67908

Other (OTH) AF: 0.285 AC: 604 AN: 2116

Alfa AF: 0.233 Hom.: 15716

Bravo AF: 0.321

Asia WGS AF: 0.323 AC: 1120 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	3.4
DANN	Benign	0.54
PhyloP100		-1.7
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: rs9465871; hg19: chr6-20717255;