chr6-21065595-T-C

Variant names:

• chr6-21065595-T-C
• rs4712580
• NM_017774.3:c.1236+367T>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.1236+367T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.845 in 150,980 control chromosomes in the GnomAD database, including 54,317 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 0.84 (54317 hom., cov: 26)
• Consequence: CDKAL1 NM_017774.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.686
• Publications: 6 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=-0.97).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.939 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_017774.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CDKAL1	NM_017774.3	MANE Select	c.1236+367T>C		intron	N/A	NP_060244.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CDKAL1	ENST00000274695.8	TSL:1 MANE Select	c.1236+367T>C		intron	N/A	ENSP00000274695.4
	CDKAL1	ENST00000378610.1	TSL:2	c.1236+367T>C		intron	N/A	ENSP00000367873.1

Frequencies

GnomAD3 genomes AF: 0.844 AC: 127404 AN: 150868 Hom.: 54257 Cov.: 26

Gnomad AFR AF: 0.947

Gnomad AMI AF: 0.932

Gnomad AMR AF: 0.872

Gnomad ASJ AF: 0.845

Gnomad EAS AF: 0.613

Gnomad SAS AF: 0.755

Gnomad FIN AF: 0.782

Gnomad MID AF: 0.942

Gnomad NFE AF: 0.807

Gnomad OTH AF: 0.863

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

GnomAD4 genome AF: 0.845 AC: 127518 AN: 150980 Hom.: 54317 Cov.: 26 AF XY: 0.841 AC XY: 61910 AN XY: 73622

African (AFR) AF: 0.947 AC: 38946 AN: 41126

American (AMR) AF: 0.873 AC: 13269 AN: 15204

Ashkenazi Jewish (ASJ) AF: 0.845 AC: 2930 AN: 3468

East Asian (EAS) AF: 0.613 AC: 3120 AN: 5092

South Asian (SAS) AF: 0.757 AC: 3590 AN: 4744

European-Finnish (FIN) AF: 0.782 AC: 7991 AN: 10220

Middle Eastern (MID) AF: 0.941 AC: 273 AN: 290

European-Non Finnish (NFE) AF: 0.807 AC: 54733 AN: 67818

Other (OTH) AF: 0.862 AC: 1816 AN: 2106

Alfa AF: 0.822 Hom.: 78601

Bravo AF: 0.859

Asia WGS AF: 0.705 AC: 2454 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	1.2
DANN	Benign	0.55
PhyloP100		-0.69
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: rs4712580; hg19: chr6-21065826;