rs12190631

Positions:

• chr6-20912441-C-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The ENST00000274695.8(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 ENST00000274695.8 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.526

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=-0.71).
• 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 male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 56 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CDKAL1	NM_017774.3	c.743-42978C>G		intron_variant		ENST00000274695.8	NP_060244.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CDKAL1	ENST00000274695.8	c.743-42978C>G		intron_variant		1	NM_017774.3	ENSP00000274695	P1
CDKAL1	ENST00000378610.1	c.743-42978C>G		intron_variant		2		ENSP00000367873	P1

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

Gnomad4 AFR AF: 0.00701

Gnomad4 AMR AF: 0.0136

Gnomad4 ASJ AF: 0.00806

Gnomad4 EAS AF: 0.00155

Gnomad4 SAS AF: 0.00748

Gnomad4 FIN AF: 0.0194

Gnomad4 NFE AF: 0.0405

Gnomad4 OTH AF: 0.0208

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

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: rs12190631; hg19: chr6-20912672;