rs12190631

Variant names:

• chr6-20912441-C-G
• rs12190631
• NM_017774.3:c.743-42978C>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_017774.3(CDKAL1):​c.743-42978C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0235 in 152,128 control chromosomes in the GnomAD database, including 56 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 0.024 (56 hom., cov: 33)
• Consequence: CDKAL1 NM_017774.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.526
• Publications: 1 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=-0.71).
• BS1: Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.0235 (3578/152128) while in subpopulation NFE AF = 0.0405 (2751/67996). AF 95% confidence interval is 0.0392. There are 56 homozygotes in GnomAd4. There are 1574 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 56 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CDKAL1	NM_017774.3	c.743-42978C>G		intron_variant	Intron 9 of 15	ENST00000274695.8	NP_060244.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CDKAL1	ENST00000274695.8	c.743-42978C>G		intron_variant	Intron 9 of 15	1	NM_017774.3	ENSP00000274695.4
CDKAL1	ENST00000378610.1	c.743-42978C>G		intron_variant	Intron 7 of 13	2		ENSP00000367873.1

Frequencies

GnomAD3 genomes AF: 0.0235 AC: 3579 AN: 152010 Hom.: 56 Cov.: 33

Gnomad AFR AF: 0.00703

Gnomad AMI AF: 0.00658

Gnomad AMR AF: 0.0136

Gnomad ASJ AF: 0.00806

Gnomad EAS AF: 0.00154

Gnomad SAS AF: 0.00768

Gnomad FIN AF: 0.0194

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.0405

Gnomad OTH AF: 0.0211

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

GnomAD4 genome AF: 0.0235 AC: 3578 AN: 152128 Hom.: 56 Cov.: 33 AF XY: 0.0212 AC XY: 1574 AN XY: 74376

African (AFR) AF: 0.00701 AC: 291 AN: 41490

American (AMR) AF: 0.0136 AC: 208 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.00806 AC: 28 AN: 3472

East Asian (EAS) AF: 0.00155 AC: 8 AN: 5168

South Asian (SAS) AF: 0.00748 AC: 36 AN: 4814

European-Finnish (FIN) AF: 0.0194 AC: 205 AN: 10592

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.0405 AC: 2751 AN: 67996

Other (OTH) AF: 0.0208 AC: 44 AN: 2112

Alfa AF: 0.0323 Hom.: 11

Bravo AF: 0.0226

Asia WGS AF: 0.00202 AC: 7 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.71
CADD	Benign	7.8
DANN	Benign	0.82
PhyloP100		-0.53
Mutation Taster		=100/0	polymorphism

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: rs12190631; hg19: chr6-20912672;