6-20661019-G-C

Variant names:

• chr6-20661019-G-C
• rs7754840
• NM_017774.3:c.371+11642G>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.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
• Publications: 339 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=-0.92).
• 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 rank	MANE	Protein	UniProt
CDKAL1	NM_017774.3	c.371+11642G>C		intron_variant	Intron 5 of 15	ENST00000274695.8	NP_060244.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CDKAL1	ENST00000274695.8	c.371+11642G>C		intron_variant	Intron 5 of 15	1	NM_017774.3	ENSP00000274695.4
CDKAL1	ENST00000378610.1	c.371+11642G>C		intron_variant	Intron 3 of 13	2		ENSP00000367873.1

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

African (AFR) AF: 0.583 AC: 24127 AN: 41392

American (AMR) AF: 0.325 AC: 4954 AN: 15250

Ashkenazi Jewish (ASJ) AF: 0.346 AC: 1199 AN: 3470

East Asian (EAS) AF: 0.388 AC: 1997 AN: 5146

South Asian (SAS) AF: 0.267 AC: 1285 AN: 4820

European-Finnish (FIN) AF: 0.373 AC: 3929 AN: 10526

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

European-Non Finnish (NFE) AF: 0.315 AC: 21415 AN: 67910

Other (OTH) AF: 0.365 AC: 768 AN: 2104

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

Dec 26, 2019

Department of Endocrinology, The Second Hospital of Jilin University

Significance: risk factor

Review Status: no assertion criteria provided

Collection Method: clinical testing

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
PhyloP100		-0.55
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: rs7754840; hg19: chr6-20661250;