rs9295479

Positions:

• chr6-20735807-T-A

Variant summary

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

The NM_017774.3(CDKAL1):​c.372-3712T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.194 in 152,196 control chromosomes in the GnomAD database, including 3,317 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 (3317 hom., cov: 32)
• Consequence: CDKAL1 NM_017774.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.49

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=-0.82).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.327 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CDKAL1	NM_017774.3	c.372-3712T>A		intron_variant		ENST00000274695.8	NP_060244.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CDKAL1	ENST00000274695.8	c.372-3712T>A		intron_variant		1	NM_017774.3	ENSP00000274695	P1
CDKAL1	ENST00000378610.1	c.372-3712T>A		intron_variant		2		ENSP00000367873	P1

Frequencies

GnomAD3 genomes AF: 0.193 AC: 29424 AN: 152078 Hom.: 3312 Cov.: 32

Gnomad AFR AF: 0.0879

Gnomad AMI AF: 0.291

Gnomad AMR AF: 0.220

Gnomad ASJ AF: 0.190

Gnomad EAS AF: 0.340

Gnomad SAS AF: 0.306

Gnomad FIN AF: 0.294

Gnomad MID AF: 0.149

Gnomad NFE AF: 0.217

Gnomad OTH AF: 0.174

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

GnomAD4 genome AF: 0.194 AC: 29458 AN: 152196 Hom.: 3317 Cov.: 32 AF XY: 0.200 AC XY: 14885 AN XY: 74402

Gnomad4 AFR AF: 0.0882

Gnomad4 AMR AF: 0.221

Gnomad4 ASJ AF: 0.190

Gnomad4 EAS AF: 0.340

Gnomad4 SAS AF: 0.307

Gnomad4 FIN AF: 0.294

Gnomad4 NFE AF: 0.217

Gnomad4 OTH AF: 0.173

Alfa AF: 0.209 Hom.: 453

Bravo AF: 0.182

Asia WGS AF: 0.308 AC: 1075 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	5.8
DANN	Benign	0.70
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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

Publications

LitVar

Other links and lift over

dbSNP: rs9295479; hg19: chr6-20736038;