rs9465948

chr6-21023871-G-A

Variant summary

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

The NM_017774.3(CDKAL1):c.1055+23499G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.188 in 151,942 control chromosomes in the GnomAD database, including 2,842 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 (2842 hom., cov: 32)
• Consequence: CDKAL1 NM_017774.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.312

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=-0.81).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.309 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CDKAL1	NM_017774.3	c.1055+23499G>A		intron_variant		ENST00000274695.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CDKAL1	ENST00000274695.8	c.1055+23499G>A		intron_variant		1	NM_017774.3	P1
CDKAL1	ENST00000378610.1	c.1055+23499G>A		intron_variant		2		P1

Frequencies

GnomAD3 genomes AF: 0.188 AC: 28490 AN: 151824 Hom.: 2838 Cov.: 32

Gnomad AFR AF: 0.210

Gnomad AMI AF: 0.227

Gnomad AMR AF: 0.156

Gnomad ASJ AF: 0.161

Gnomad EAS AF: 0.153

Gnomad SAS AF: 0.321

Gnomad FIN AF: 0.238

Gnomad MID AF: 0.203

Gnomad NFE AF: 0.167

Gnomad OTH AF: 0.183

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

GnomAD4 genome AF: 0.188 AC: 28516 AN: 151942 Hom.: 2842 Cov.: 32 AF XY: 0.194 AC XY: 14407 AN XY: 74264

Gnomad4 AFR AF: 0.210

Gnomad4 AMR AF: 0.156

Gnomad4 ASJ AF: 0.161

Gnomad4 EAS AF: 0.153

Gnomad4 SAS AF: 0.322

Gnomad4 FIN AF: 0.238

Gnomad4 NFE AF: 0.167

Gnomad4 OTH AF: 0.187

Alfa AF: 0.172 Hom.: 517

Bravo AF: 0.179

Asia WGS AF: 0.246 AC: 855 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
Cadd	Benign	4.3
Dann	Benign	0.78

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: rs9465948; hg19: chr6-21024102;