6-21118008-G-C

Variant names:

• chr6-21118008-G-C
• rs4389757
• NM_017774.3:c.1299+9545G>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.1299+9545G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.114 in 152,098 control chromosomes in the GnomAD database, including 1,017 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 0.11 (1017 hom., cov: 32)
• Consequence: CDKAL1 NM_017774.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.65

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=-0.9).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.12 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CDKAL1	NM_017774.3	c.1299+9545G>C		intron_variant	Intron 13 of 15	ENST00000274695.8	NP_060244.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CDKAL1	ENST00000274695.8	c.1299+9545G>C		intron_variant	Intron 13 of 15	1	NM_017774.3	ENSP00000274695.4
CDKAL1	ENST00000378610.1	c.1299+9545G>C		intron_variant	Intron 11 of 13	2		ENSP00000367873.1

Frequencies

GnomAD3 genomes AF: 0.114 AC: 17286 AN: 151980 Hom.: 1016 Cov.: 32

Gnomad AFR AF: 0.119

Gnomad AMI AF: 0.135

Gnomad AMR AF: 0.0873

Gnomad ASJ AF: 0.163

Gnomad EAS AF: 0.00540

Gnomad SAS AF: 0.100

Gnomad FIN AF: 0.116

Gnomad MID AF: 0.139

Gnomad NFE AF: 0.122

Gnomad OTH AF: 0.117

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

GnomAD4 genome AF: 0.114 AC: 17295 AN: 152098 Hom.: 1017 Cov.: 32 AF XY: 0.111 AC XY: 8223 AN XY: 74354

African (AFR) AF: 0.119 AC: 4936 AN: 41486

American (AMR) AF: 0.0872 AC: 1331 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.163 AC: 564 AN: 3470

East Asian (EAS) AF: 0.00561 AC: 29 AN: 5172

South Asian (SAS) AF: 0.101 AC: 484 AN: 4814

European-Finnish (FIN) AF: 0.116 AC: 1225 AN: 10576

Middle Eastern (MID) AF: 0.143 AC: 42 AN: 294

European-Non Finnish (NFE) AF: 0.122 AC: 8316 AN: 67988

Other (OTH) AF: 0.116 AC: 245 AN: 2116

Alfa AF: 0.0393 Hom.: 42

Bravo AF: 0.112

Asia WGS AF: 0.0500 AC: 174 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	13
DANN	Benign	0.66
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

Publications

LitVar

Other links and lift over

dbSNP: rs4389757; hg19: chr6-21118239;