6-20631314-A-T

Variant names:

• chr6-20631314-A-T
• rs2328528
• NM_017774.3:c.287-17979A>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.287-17979A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.19 in 152,030 control chromosomes in the GnomAD database, including 2,846 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 0.19 (2846 hom., cov: 32)
• Consequence: CDKAL1 NM_017774.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.114
• 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]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.357 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.287-17979A>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.287-17979A>T		intron	N/A	ENSP00000274695.4
	CDKAL1	ENST00000378610.1	TSL:2	c.287-17979A>T		intron	N/A	ENSP00000367873.1

Frequencies

GnomAD3 genomes AF: 0.190 AC: 28834 AN: 151912 Hom.: 2846 Cov.: 32

Gnomad AFR AF: 0.187

Gnomad AMI AF: 0.236

Gnomad AMR AF: 0.168

Gnomad ASJ AF: 0.185

Gnomad EAS AF: 0.372

Gnomad SAS AF: 0.232

Gnomad FIN AF: 0.232

Gnomad MID AF: 0.212

Gnomad NFE AF: 0.173

Gnomad OTH AF: 0.193

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

GnomAD4 genome AF: 0.190 AC: 28840 AN: 152030 Hom.: 2846 Cov.: 32 AF XY: 0.193 AC XY: 14340 AN XY: 74304

African (AFR) AF: 0.187 AC: 7739 AN: 41488

American (AMR) AF: 0.168 AC: 2565 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.185 AC: 642 AN: 3468

East Asian (EAS) AF: 0.371 AC: 1906 AN: 5140

South Asian (SAS) AF: 0.233 AC: 1122 AN: 4824

European-Finnish (FIN) AF: 0.232 AC: 2444 AN: 10546

Middle Eastern (MID) AF: 0.207 AC: 61 AN: 294

European-Non Finnish (NFE) AF: 0.173 AC: 11735 AN: 67952

Other (OTH) AF: 0.195 AC: 411 AN: 2110

Alfa AF: 0.182 Hom.: 315

Bravo AF: 0.183

Asia WGS AF: 0.261 AC: 907 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	4.7
DANN	Benign	0.79
PhyloP100		0.11
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: rs2328528; hg19: chr6-20631545;