rs9295479

Variant names:

• chr6-20735807-T-A
• rs9295479
• NM_017774.3:c.372-3712T>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.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
• Publications: 5 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=-0.82).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.327 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CDKAL1	NM_017774.3	MANE Select	c.372-3712T>A		intron	N/A	NP_060244.2	Q5VV42-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CDKAL1	ENST00000274695.8	TSL:1 MANE Select	c.372-3712T>A		intron	N/A	ENSP00000274695.4	Q5VV42-1
	CDKAL1	ENST00000946780.1		c.372-3712T>A		intron	N/A	ENSP00000616839.1
	CDKAL1	ENST00000378610.1	TSL:2	c.372-3712T>A		intron	N/A	ENSP00000367873.1	Q5VV42-1

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

African (AFR) AF: 0.0882 AC: 3664 AN: 41550

American (AMR) AF: 0.221 AC: 3374 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.190 AC: 661 AN: 3472

East Asian (EAS) AF: 0.340 AC: 1760 AN: 5176

South Asian (SAS) AF: 0.307 AC: 1481 AN: 4826

European-Finnish (FIN) AF: 0.294 AC: 3109 AN: 10578

Middle Eastern (MID) AF: 0.167 AC: 49 AN: 294

European-Non Finnish (NFE) AF: 0.217 AC: 14729 AN: 67984

Other (OTH) AF: 0.173 AC: 366 AN: 2114

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	5.8
DANN	Benign	0.70
PhyloP100		1.5
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
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: rs9295479; hg19: chr6-20736038;