rs4389757

chr6-21118008-G-Cchr6-21118008-G-T

Variant summary

Our verdict is Benign. Variant got -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

Verdict is Benign. Variant got -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/exons	MANE	UniProt
CDKAL1	NM_017774.3	c.1299+9545G>C		intron_variant		ENST00000274695.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CDKAL1	ENST00000274695.8	c.1299+9545G>C		intron_variant		1	NM_017774.3	P1
CDKAL1	ENST00000378610.1	c.1299+9545G>C		intron_variant		2		P1

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

Gnomad4 AFR AF: 0.119

Gnomad4 AMR AF: 0.0872

Gnomad4 ASJ AF: 0.163

Gnomad4 EAS AF: 0.00561

Gnomad4 SAS AF: 0.101

Gnomad4 FIN AF: 0.116

Gnomad4 NFE AF: 0.122

Gnomad4 OTH AF: 0.116

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

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;