6-21231243-C-T

Variant names:

• chr6-21231243-C-T
• rs1563727
• NM_017774.3:c.*204C>T

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_017774.3(CDKAL1):​c.*204C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000955 in 419,064 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 0.000086 (0 hom., cov: 31)
  • Exomes 𝑓: 0.00010 (0 hom.)
• Consequence: CDKAL1 NM_017774.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0100
• Publications: 4 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]

ENSG00000287404 (HGNC:):

ACMG classification

Our verdict: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.74).

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.*204C>T		3_prime_UTR	Exon 16 of 16	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.*204C>T		3_prime_UTR	Exon 16 of 16	ENSP00000274695.4	Q5VV42-1
	CDKAL1	ENST00000946780.1		c.*204C>T		3_prime_UTR	Exon 17 of 17	ENSP00000616839.1
	CDKAL1	ENST00000378610.1	TSL:2	c.*204C>T		3_prime_UTR	Exon 14 of 14	ENSP00000367873.1	Q5VV42-1

Frequencies

GnomAD3 genomes AF: 0.0000856 AC: 13 AN: 151854 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.0000242

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000208

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000162

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.000101 AC: 27 AN: 267092 Hom.: 0 Cov.: 3 AF XY: 0.0000955 AC XY: 13 AN XY: 136110

African (AFR) AF: 0.00 AC: 0 AN: 8552

American (AMR) AF: 0.000103 AC: 1 AN: 9720

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 9706

East Asian (EAS) AF: 0.0000408 AC: 1 AN: 24504

South Asian (SAS) AF: 0.00 AC: 0 AN: 6934

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 20690

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 1316

European-Non Finnish (NFE) AF: 0.000148 AC: 25 AN: 168566

Other (OTH) AF: 0.00 AC: 0 AN: 17104

GnomAD4 genome AF: 0.0000855 AC: 13 AN: 151972 Hom.: 0 Cov.: 31 AF XY: 0.0000269 AC XY: 2 AN XY: 74250

African (AFR) AF: 0.0000241 AC: 1 AN: 41426

American (AMR) AF: 0.00 AC: 0 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5172

South Asian (SAS) AF: 0.000208 AC: 1 AN: 4804

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10530

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000162 AC: 11 AN: 67970

Other (OTH) AF: 0.00 AC: 0 AN: 2112

Alfa AF: 0.00 Hom.: 1452

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.74
CADD	Benign	5.1
DANN	Benign	0.93
PhyloP100		0.010

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: rs1563727; hg19: chr6-21231474;