6-20641105-C-T

Variant names:

• chr6-20641105-C-T
• rs9348440
• NM_017774.3:c.287-8188C>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.287-8188C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.137 in 152,014 control chromosomes in the GnomAD database, including 1,637 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 0.14 (1637 hom., cov: 32)
• Consequence: CDKAL1 NM_017774.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.588
• Publications: 22 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=-0.74).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.368 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CDKAL1	NM_017774.3	c.287-8188C>T		intron_variant	Intron 4 of 15	ENST00000274695.8	NP_060244.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CDKAL1	ENST00000274695.8	c.287-8188C>T		intron_variant	Intron 4 of 15	1	NM_017774.3	ENSP00000274695.4
CDKAL1	ENST00000378610.1	c.287-8188C>T		intron_variant	Intron 2 of 13	2		ENSP00000367873.1

Frequencies

GnomAD3 genomes AF: 0.137 AC: 20780 AN: 151894 Hom.: 1637 Cov.: 32

Gnomad AFR AF: 0.105

Gnomad AMI AF: 0.164

Gnomad AMR AF: 0.134

Gnomad ASJ AF: 0.141

Gnomad EAS AF: 0.383

Gnomad SAS AF: 0.208

Gnomad FIN AF: 0.155

Gnomad MID AF: 0.174

Gnomad NFE AF: 0.129

Gnomad OTH AF: 0.141

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

GnomAD4 genome AF: 0.137 AC: 20771 AN: 152014 Hom.: 1637 Cov.: 32 AF XY: 0.140 AC XY: 10432 AN XY: 74318

African (AFR) AF: 0.105 AC: 4336 AN: 41466

American (AMR) AF: 0.134 AC: 2046 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.141 AC: 488 AN: 3464

East Asian (EAS) AF: 0.382 AC: 1976 AN: 5170

South Asian (SAS) AF: 0.208 AC: 1001 AN: 4814

European-Finnish (FIN) AF: 0.155 AC: 1632 AN: 10554

Middle Eastern (MID) AF: 0.170 AC: 50 AN: 294

European-Non Finnish (NFE) AF: 0.129 AC: 8794 AN: 67966

Other (OTH) AF: 0.141 AC: 298 AN: 2114

Alfa AF: 0.136 Hom.: 3204

Bravo AF: 0.132

Asia WGS AF: 0.250 AC: 866 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.74
CADD	Benign	14
DANN	Benign	0.75
PhyloP100		0.59
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: rs9348440; hg19: chr6-20641336;