6-20731293-A-C

Variant names:

• chr6-20731293-A-C
• rs7741604
• NM_017774.3:c.372-8226A>C

Variant summary

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

The NM_017774.3(CDKAL1):​c.372-8226A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.121 in 152,204 control chromosomes in the GnomAD database, including 1,574 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 0.12 (1574 hom., cov: 32)
• Consequence: CDKAL1 NM_017774.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.00500

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=-0.93).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.397 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CDKAL1	NM_017774.3	c.372-8226A>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.372-8226A>C		intron_variant	Intron 5 of 15	1	NM_017774.3	ENSP00000274695.4
CDKAL1	ENST00000378610.1	c.372-8226A>C		intron_variant	Intron 3 of 13	2		ENSP00000367873.1

Frequencies

GnomAD3 genomes AF: 0.121 AC: 18378 AN: 152086 Hom.: 1582 Cov.: 32

Gnomad AFR AF: 0.0272

Gnomad AMI AF: 0.0439

Gnomad AMR AF: 0.135

Gnomad ASJ AF: 0.128

Gnomad EAS AF: 0.412

Gnomad SAS AF: 0.189

Gnomad FIN AF: 0.180

Gnomad MID AF: 0.165

Gnomad NFE AF: 0.139

Gnomad OTH AF: 0.123

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

GnomAD4 genome AF: 0.121 AC: 18352 AN: 152204 Hom.: 1574 Cov.: 32 AF XY: 0.127 AC XY: 9449 AN XY: 74422

Gnomad4 AFR AF: 0.0271

Gnomad4 AMR AF: 0.135

Gnomad4 ASJ AF: 0.128

Gnomad4 EAS AF: 0.411

Gnomad4 SAS AF: 0.188

Gnomad4 FIN AF: 0.180

Gnomad4 NFE AF: 0.139

Gnomad4 OTH AF: 0.122

Alfa AF: 0.136 Hom.: 2093

Bravo AF: 0.115

Asia WGS AF: 0.249 AC: 864 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	1.5
DANN	Benign	0.72

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: rs7741604; hg19: chr6-20731524;