6-20663401-T-G

Variant names:

• chr6-20663401-T-G
• rs9460546
• NM_017774.3:c.371+14024T>G

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+14024T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.396 in 151,822 control chromosomes in the GnomAD database, including 13,034 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 0.40 (13034 hom., cov: 31)
• Consequence: CDKAL1 NM_017774.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.493
• Publications: 29 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 (AFR) allele frequency at 95% confidence interval = 0.577 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CDKAL1	NM_017774.3	MANE Select	c.371+14024T>G		intron	N/A	NP_060244.2	Q5VV42-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CDKAL1	ENST00000274695.8	TSL:1 MANE Select	c.371+14024T>G		intron	N/A	ENSP00000274695.4	Q5VV42-1
	CDKAL1	ENST00000946780.1		c.371+14024T>G		intron	N/A	ENSP00000616839.1
	CDKAL1	ENST00000378610.1	TSL:2	c.371+14024T>G		intron	N/A	ENSP00000367873.1	Q5VV42-1

Frequencies

GnomAD3 genomes AF: 0.396 AC: 60074 AN: 151704 Hom.: 13023 Cov.: 31

Gnomad AFR AF: 0.584

Gnomad AMI AF: 0.376

Gnomad AMR AF: 0.325

Gnomad ASJ AF: 0.346

Gnomad EAS AF: 0.389

Gnomad SAS AF: 0.266

Gnomad FIN AF: 0.372

Gnomad MID AF: 0.339

Gnomad NFE AF: 0.315

Gnomad OTH AF: 0.364

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

GnomAD4 genome AF: 0.396 AC: 60113 AN: 151822 Hom.: 13034 Cov.: 31 AF XY: 0.395 AC XY: 29287 AN XY: 74160

African (AFR) AF: 0.583 AC: 24147 AN: 41388

American (AMR) AF: 0.324 AC: 4934 AN: 15218

Ashkenazi Jewish (ASJ) AF: 0.346 AC: 1200 AN: 3470

East Asian (EAS) AF: 0.388 AC: 2000 AN: 5152

South Asian (SAS) AF: 0.267 AC: 1284 AN: 4812

European-Finnish (FIN) AF: 0.372 AC: 3929 AN: 10550

Middle Eastern (MID) AF: 0.337 AC: 99 AN: 294

European-Non Finnish (NFE) AF: 0.315 AC: 21409 AN: 67918

Other (OTH) AF: 0.364 AC: 769 AN: 2110

Alfa AF: 0.403 Hom.: 6168

Bravo AF: 0.400

Asia WGS AF: 0.330 AC: 1145 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.18
DANN	Benign	0.44
PhyloP100		-0.49
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: rs9460546; hg19: chr6-20663632;