6-20661019-G-C

Position:

• chr6-20661019-G-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_017774.3(CDKAL1):​c.371+11642G>C 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 151,824 control chromosomes in the GnomAD database, including 13,023 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as risk factor (no stars).

• Frequency: Genomes: 𝑓 0.40 (13023 hom., cov: 31)
• Consequence: CDKAL1 NM_017774.3 intron
• Clinical Significance: risk factor no assertion criteria provided O:1
• Conservation: PhyloP100: -0.551

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=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.577 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CDKAL1	NM_017774.3	c.371+11642G>C		intron_variant		ENST00000274695.8	NP_060244.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CDKAL1	ENST00000274695.8	c.371+11642G>C		intron_variant		1	NM_017774.3	ENSP00000274695	P1
CDKAL1	ENST00000378610.1	c.371+11642G>C		intron_variant		2		ENSP00000367873	P1

Frequencies

GnomAD3 genomes AF: 0.396 AC: 60078 AN: 151704 Hom.: 13012 Cov.: 31

Gnomad AFR AF: 0.583

Gnomad AMI AF: 0.377

Gnomad AMR AF: 0.325

Gnomad ASJ AF: 0.346

Gnomad EAS AF: 0.389

Gnomad SAS AF: 0.266

Gnomad FIN AF: 0.373

Gnomad MID AF: 0.341

Gnomad NFE AF: 0.315

Gnomad OTH AF: 0.365

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

GnomAD4 genome AF: 0.396 AC: 60117 AN: 151824 Hom.: 13023 Cov.: 31 AF XY: 0.395 AC XY: 29317 AN XY: 74216

Gnomad4 AFR AF: 0.583

Gnomad4 AMR AF: 0.325

Gnomad4 ASJ AF: 0.346

Gnomad4 EAS AF: 0.388

Gnomad4 SAS AF: 0.267

Gnomad4 FIN AF: 0.373

Gnomad4 NFE AF: 0.315

Gnomad4 OTH AF: 0.365

Alfa AF: 0.309 Hom.: 4064

Bravo AF: 0.400

Asia WGS AF: 0.331 AC: 1147 AN: 3476

ClinVar

Significance: risk factor

Submissions summary: Other:1

Revision: no assertion criteria provided

Submissions by phenotype

Obesity Other:1

risk factor, no assertion criteria provided

clinical testing

Department of Endocrinology, The Second Hospital of Jilin University

Dec 26, 2019

We found that loci CDKAL1 (rs7754840) may be associated with obesity-related indicators. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.49
DANN	Benign	0.40

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: rs7754840; hg19: chr6-20661250;