6-20725192-G-C

Position:

• chr6-20725192-G-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_017774.3(CDKAL1):​c.372-14327G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.336 in 151,360 control chromosomes in the GnomAD database, including 10,311 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 0.34 (10311 hom., cov: 29)
• Consequence: CDKAL1 NM_017774.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.359

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=-0.94).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.559 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CDKAL1	NM_017774.3	c.372-14327G>C		intron_variant		ENST00000274695.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CDKAL1	ENST00000274695.8	c.372-14327G>C		intron_variant		1	NM_017774.3	P1
CDKAL1	ENST00000378610.1	c.372-14327G>C		intron_variant		2		P1

Frequencies

GnomAD3 genomes AF: 0.336 AC: 50854 AN: 151242 Hom.: 10295 Cov.: 29

Gnomad AFR AF: 0.565

Gnomad AMI AF: 0.311

Gnomad AMR AF: 0.294

Gnomad ASJ AF: 0.314

Gnomad EAS AF: 0.455

Gnomad SAS AF: 0.269

Gnomad FIN AF: 0.191

Gnomad MID AF: 0.370

Gnomad NFE AF: 0.227

Gnomad OTH AF: 0.335

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

GnomAD4 genome AF: 0.336 AC: 50903 AN: 151360 Hom.: 10311 Cov.: 29 AF XY: 0.334 AC XY: 24678 AN XY: 73932

Gnomad4 AFR AF: 0.565

Gnomad4 AMR AF: 0.294

Gnomad4 ASJ AF: 0.314

Gnomad4 EAS AF: 0.454

Gnomad4 SAS AF: 0.269

Gnomad4 FIN AF: 0.191

Gnomad4 NFE AF: 0.227

Gnomad4 OTH AF: 0.332

Alfa AF: 0.236 Hom.: 2547

Bravo AF: 0.358

Asia WGS AF: 0.320 AC: 1109 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	1.3
DANN	Benign	0.69

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: rs7747752; hg19: chr6-20725423;