chr6-20592753-C-T

Variant names:

• chr6-20592753-C-T
• rs62400067
• NM_017774.3:c.286+44048C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_017774.3(CDKAL1):​c.286+44048C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0643 in 152,118 control chromosomes in the GnomAD database, including 334 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 0.064 (334 hom., cov: 32)
• Consequence: CDKAL1 NM_017774.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.288
• Publications: 2 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 = 0.0805 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CDKAL1	NM_017774.3	MANE Select	c.286+44048C>T		intron	N/A	NP_060244.2	Q5VV42-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CDKAL1	ENST00000274695.8	TSL:1 MANE Select	c.286+44048C>T		intron	N/A	ENSP00000274695.4	Q5VV42-1
	CDKAL1	ENST00000946780.1		c.286+44048C>T		intron	N/A	ENSP00000616839.1
	CDKAL1	ENST00000378610.1	TSL:2	c.286+44048C>T		intron	N/A	ENSP00000367873.1	Q5VV42-1

Frequencies

GnomAD3 genomes AF: 0.0643 AC: 9781 AN: 152000 Hom.: 333 Cov.: 32

Gnomad AFR AF: 0.0828

Gnomad AMI AF: 0.0186

Gnomad AMR AF: 0.0589

Gnomad ASJ AF: 0.0818

Gnomad EAS AF: 0.00193

Gnomad SAS AF: 0.0373

Gnomad FIN AF: 0.0392

Gnomad MID AF: 0.101

Gnomad NFE AF: 0.0643

Gnomad OTH AF: 0.0700

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

GnomAD4 genome AF: 0.0643 AC: 9788 AN: 152118 Hom.: 334 Cov.: 32 AF XY: 0.0614 AC XY: 4563 AN XY: 74358

African (AFR) AF: 0.0828 AC: 3434 AN: 41490

American (AMR) AF: 0.0587 AC: 897 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.0818 AC: 284 AN: 3470

East Asian (EAS) AF: 0.00193 AC: 10 AN: 5176

South Asian (SAS) AF: 0.0376 AC: 181 AN: 4818

European-Finnish (FIN) AF: 0.0392 AC: 415 AN: 10576

Middle Eastern (MID) AF: 0.102 AC: 30 AN: 294

European-Non Finnish (NFE) AF: 0.0643 AC: 4374 AN: 68002

Other (OTH) AF: 0.0693 AC: 146 AN: 2108

Alfa AF: 0.0228 Hom.: 13

Bravo AF: 0.0667

Asia WGS AF: 0.0200 AC: 68 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	4.9
DANN	Benign	0.51
PhyloP100		0.29
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: rs62400067; hg19: chr6-20592984;