6-20660803-A-C

Position:

• chr6-20660803-A-C

Variant summary

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

The NM_017774.3(CDKAL1):​c.371+11426A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.396 in 151,990 control chromosomes in the GnomAD database, including 13,060 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (no stars).

• Frequency: Genomes: 𝑓 0.40 (13060 hom., cov: 32)
• Consequence: CDKAL1 NM_017774.3 intron
• Clinical Significance: Uncertain significance no assertion criteria provided U:1
• Conservation: PhyloP100: -0.132

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=-0.97).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.577 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CDKAL1	NM_017774.3	c.371+11426A>C		intron_variant		ENST00000274695.8	NP_060244.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CDKAL1	ENST00000274695.8	c.371+11426A>C		intron_variant		1	NM_017774.3	ENSP00000274695	P1
CDKAL1	ENST00000378610.1	c.371+11426A>C		intron_variant		2		ENSP00000367873	P1

Frequencies

GnomAD3 genomes AF: 0.396 AC: 60170 AN: 151872 Hom.: 13049 Cov.: 32

Gnomad AFR AF: 0.584

Gnomad AMI AF: 0.377

Gnomad AMR AF: 0.325

Gnomad ASJ AF: 0.345

Gnomad EAS AF: 0.389

Gnomad SAS AF: 0.266

Gnomad FIN AF: 0.373

Gnomad MID AF: 0.341

Gnomad NFE AF: 0.316

Gnomad OTH AF: 0.365

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

GnomAD4 genome AF: 0.396 AC: 60209 AN: 151990 Hom.: 13060 Cov.: 32 AF XY: 0.395 AC XY: 29356 AN XY: 74284

Gnomad4 AFR AF: 0.583

Gnomad4 AMR AF: 0.325

Gnomad4 ASJ AF: 0.345

Gnomad4 EAS AF: 0.388

Gnomad4 SAS AF: 0.267

Gnomad4 FIN AF: 0.373

Gnomad4 NFE AF: 0.315

Gnomad4 OTH AF: 0.365

Alfa AF: 0.325 Hom.: 11318

Bravo AF: 0.400

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: no assertion criteria provided

Submissions by phenotype

Type 2 diabetes mellitus Uncertain:1

Uncertain significance, no assertion criteria provided

literature only

OMIM

Sep 01, 2014

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	4.0
DANN	Benign	0.42

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: rs10946398; hg19: chr6-20661034;