6-21023871-G-A

Variant names:

• chr6-21023871-G-A
• rs9465948
• NM_017774.3:c.1055+23499G>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 3 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=-0.81).
• 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 rank	MANE	Protein	UniProt
CDKAL1	NM_017774.3	c.1055+23499G>A		intron_variant	Intron 11 of 15	ENST00000274695.8	NP_060244.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CDKAL1	ENST00000274695.8	c.1055+23499G>A		intron_variant	Intron 11 of 15	1	NM_017774.3	ENSP00000274695.4
CDKAL1	ENST00000378610.1	c.1055+23499G>A		intron_variant	Intron 9 of 13	2		ENSP00000367873.1

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

African (AFR) AF: 0.210 AC: 8705 AN: 41436

American (AMR) AF: 0.156 AC: 2379 AN: 15240

Ashkenazi Jewish (ASJ) AF: 0.161 AC: 560 AN: 3468

East Asian (EAS) AF: 0.153 AC: 792 AN: 5170

South Asian (SAS) AF: 0.322 AC: 1550 AN: 4810

European-Finnish (FIN) AF: 0.238 AC: 2501 AN: 10528

Middle Eastern (MID) AF: 0.197 AC: 58 AN: 294

European-Non Finnish (NFE) AF: 0.167 AC: 11370 AN: 67976

Other (OTH) AF: 0.187 AC: 394 AN: 2108

Alfa AF: 0.171 Hom.: 834

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
PhyloP100		0.31
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: rs9465948; hg19: chr6-21024102;