NM_017774.3:c.517+5376C>T

Variant names:

• chr6-20764019-C-T
• rs4351239
• NM_017774.3:c.517+5376C>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.517+5376C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.561 in 151,924 control chromosomes in the GnomAD database, including 24,290 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 0.56 (24290 hom., cov: 32)
• Consequence: CDKAL1 NM_017774.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0460
• Publications: 7 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]

ENSG00000233848 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.783 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.517+5376C>T		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.517+5376C>T		intron	N/A	ENSP00000274695.4
	CDKAL1	ENST00000378610.1	TSL:2	c.517+5376C>T		intron	N/A	ENSP00000367873.1
	ENSG00000233848	ENST00000421167.1	TSL:3	n.399-7251G>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.561 AC: 85108 AN: 151806 Hom.: 24258 Cov.: 32

Gnomad AFR AF: 0.569

Gnomad AMI AF: 0.567

Gnomad AMR AF: 0.563

Gnomad ASJ AF: 0.535

Gnomad EAS AF: 0.804

Gnomad SAS AF: 0.704

Gnomad FIN AF: 0.621

Gnomad MID AF: 0.519

Gnomad NFE AF: 0.519

Gnomad OTH AF: 0.528

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

GnomAD4 genome AF: 0.561 AC: 85191 AN: 151924 Hom.: 24290 Cov.: 32 AF XY: 0.570 AC XY: 42327 AN XY: 74256

African (AFR) AF: 0.569 AC: 23571 AN: 41440

American (AMR) AF: 0.564 AC: 8611 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.535 AC: 1857 AN: 3470

East Asian (EAS) AF: 0.803 AC: 4147 AN: 5164

South Asian (SAS) AF: 0.704 AC: 3388 AN: 4810

European-Finnish (FIN) AF: 0.621 AC: 6544 AN: 10536

Middle Eastern (MID) AF: 0.507 AC: 149 AN: 294

European-Non Finnish (NFE) AF: 0.519 AC: 35286 AN: 67928

Other (OTH) AF: 0.533 AC: 1124 AN: 2110

Alfa AF: 0.559 Hom.: 3105

Bravo AF: 0.552

Asia WGS AF: 0.768 AC: 2656 AN: 3462

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	10
DANN	Benign	0.80
PhyloP100		0.046
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: rs4351239; hg19: chr6-20764250;