6-20623803-T-C

Variant names:

• chr6-20623803-T-C
• rs7763304
• NM_017774.3:c.287-25490T>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.287-25490T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.879 in 152,060 control chromosomes in the GnomAD database, including 58,773 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 0.88 (58773 hom., cov: 31)
• Consequence: CDKAL1 NM_017774.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.409
• Publications: 8 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=-0.95).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.903 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CDKAL1	NM_017774.3	c.287-25490T>C		intron_variant	Intron 4 of 15	ENST00000274695.8	NP_060244.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CDKAL1	ENST00000274695.8	c.287-25490T>C		intron_variant	Intron 4 of 15	1	NM_017774.3	ENSP00000274695.4
CDKAL1	ENST00000378610.1	c.287-25490T>C		intron_variant	Intron 2 of 13	2		ENSP00000367873.1

Frequencies

GnomAD3 genomes AF: 0.879 AC: 133540 AN: 151942 Hom.: 58738 Cov.: 31

Gnomad AFR AF: 0.911

Gnomad AMI AF: 0.847

Gnomad AMR AF: 0.878

Gnomad ASJ AF: 0.888

Gnomad EAS AF: 0.827

Gnomad SAS AF: 0.809

Gnomad FIN AF: 0.881

Gnomad MID AF: 0.943

Gnomad NFE AF: 0.868

Gnomad OTH AF: 0.883

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

GnomAD4 genome AF: 0.879 AC: 133632 AN: 152060 Hom.: 58773 Cov.: 31 AF XY: 0.878 AC XY: 65295 AN XY: 74348

African (AFR) AF: 0.911 AC: 37806 AN: 41522

American (AMR) AF: 0.878 AC: 13404 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.888 AC: 3083 AN: 3470

East Asian (EAS) AF: 0.827 AC: 4275 AN: 5170

South Asian (SAS) AF: 0.809 AC: 3898 AN: 4818

European-Finnish (FIN) AF: 0.881 AC: 9340 AN: 10606

Middle Eastern (MID) AF: 0.939 AC: 276 AN: 294

European-Non Finnish (NFE) AF: 0.868 AC: 58921 AN: 67890

Other (OTH) AF: 0.880 AC: 1858 AN: 2112

Alfa AF: 0.872 Hom.: 31254

Bravo AF: 0.882

Asia WGS AF: 0.787 AC: 2736 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	12
DANN	Benign	0.56
PhyloP100		-0.41
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: rs7763304; hg19: chr6-20624034;