chr6-20622522-C-T

Position:

• chr6-20622522-C-T

Variant summary

Our verdict is Benign. Variant got -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

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

Verdict is Benign. Variant got -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/exons	MANE	Protein	UniProt
CDKAL1	NM_017774.3	c.287-26771C>T		intron_variant		ENST00000274695.8	NP_060244.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CDKAL1	ENST00000274695.8	c.287-26771C>T		intron_variant		1	NM_017774.3	ENSP00000274695.4
CDKAL1	ENST00000378610.1	c.287-26771C>T		intron_variant		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

Gnomad4 AFR AF: 0.531

Gnomad4 AMR AF: 0.608

Gnomad4 ASJ AF: 0.587

Gnomad4 EAS AF: 0.818

Gnomad4 SAS AF: 0.656

Gnomad4 FIN AF: 0.580

Gnomad4 NFE AF: 0.565

Gnomad4 OTH AF: 0.597

Alfa AF: 0.582 Hom.: 33963

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

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

Publications

LitVar

Other links and lift over

dbSNP: rs1569660; hg19: chr6-20622753;