rs10484634

Positions:

• chr6-20541966-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_017774.3(CDKAL1):​c.-5-4380A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0669 in 152,336 control chromosomes in the GnomAD database, including 467 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 0.067 (467 hom., cov: 33)
• Consequence: CDKAL1 NM_017774.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.79

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.125 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CDKAL1	NM_017774.3	c.-5-4380A>G		intron_variant		ENST00000274695.8	NP_060244.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CDKAL1	ENST00000274695.8	c.-5-4380A>G		intron_variant		1	NM_017774.3	ENSP00000274695	P1
CDKAL1	ENST00000613575.4	c.-5-4380A>G		intron_variant		1		ENSP00000481755

Frequencies

GnomAD3 genomes AF: 0.0669 AC: 10179 AN: 152220 Hom.: 467 Cov.: 33

Gnomad AFR AF: 0.128

Gnomad AMI AF: 0.132

Gnomad AMR AF: 0.0485

Gnomad ASJ AF: 0.0617

Gnomad EAS AF: 0.000961

Gnomad SAS AF: 0.0298

Gnomad FIN AF: 0.0195

Gnomad MID AF: 0.127

Gnomad NFE AF: 0.0479

Gnomad OTH AF: 0.0632

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

GnomAD4 genome AF: 0.0669 AC: 10190 AN: 152336 Hom.: 467 Cov.: 33 AF XY: 0.0636 AC XY: 4738 AN XY: 74498

Gnomad4 AFR AF: 0.128

Gnomad4 AMR AF: 0.0483

Gnomad4 ASJ AF: 0.0617

Gnomad4 EAS AF: 0.000963

Gnomad4 SAS AF: 0.0304

Gnomad4 FIN AF: 0.0195

Gnomad4 NFE AF: 0.0479

Gnomad4 OTH AF: 0.0625

Alfa AF: 0.0563 Hom.: 54

Bravo AF: 0.0723

Asia WGS AF: 0.0180 AC: 63 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	5.9
DANN	Benign	0.54

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs10484634; hg19: chr6-20542197;