rs10946425

Variant names:

• chr6-21018424-C-T
• rs10946425
• NM_017774.3:c.1055+18052C>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.1055+18052C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.327 in 151,972 control chromosomes in the GnomAD database, including 8,646 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 0.33 (8646 hom., cov: 32)
• Consequence: CDKAL1 NM_017774.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.417
• Publications: 8 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=-0.8).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.38 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_017774.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CDKAL1	NM_017774.3	MANE Select	c.1055+18052C>T		intron	N/A	NP_060244.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CDKAL1	ENST00000274695.8	TSL:1 MANE Select	c.1055+18052C>T		intron	N/A	ENSP00000274695.4
	CDKAL1	ENST00000378610.1	TSL:2	c.1055+18052C>T		intron	N/A	ENSP00000367873.1

Frequencies

GnomAD3 genomes AF: 0.327 AC: 49651 AN: 151854 Hom.: 8648 Cov.: 32

Gnomad AFR AF: 0.221

Gnomad AMI AF: 0.363

Gnomad AMR AF: 0.382

Gnomad ASJ AF: 0.393

Gnomad EAS AF: 0.189

Gnomad SAS AF: 0.310

Gnomad FIN AF: 0.334

Gnomad MID AF: 0.446

Gnomad NFE AF: 0.384

Gnomad OTH AF: 0.380

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

GnomAD4 genome AF: 0.327 AC: 49662 AN: 151972 Hom.: 8646 Cov.: 32 AF XY: 0.325 AC XY: 24111 AN XY: 74280

African (AFR) AF: 0.221 AC: 9178 AN: 41470

American (AMR) AF: 0.381 AC: 5826 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.393 AC: 1360 AN: 3464

East Asian (EAS) AF: 0.189 AC: 978 AN: 5174

South Asian (SAS) AF: 0.309 AC: 1488 AN: 4808

European-Finnish (FIN) AF: 0.334 AC: 3511 AN: 10522

Middle Eastern (MID) AF: 0.432 AC: 126 AN: 292

European-Non Finnish (NFE) AF: 0.384 AC: 26071 AN: 67948

Other (OTH) AF: 0.376 AC: 794 AN: 2112

Alfa AF: 0.366 Hom.: 41628

Bravo AF: 0.329

Asia WGS AF: 0.231 AC: 804 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	9.6
DANN	Benign	0.81
PhyloP100		0.42
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: rs10946425; hg19: chr6-21018655;