rs7756992

chr6-20679478-A-Gchr6-20679478-A-T

Variant summary

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

The NM_017774.3(CDKAL1):c.371+30101A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.371 in 152,020 control chromosomes in the GnomAD database, including 11,801 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 0.37 (11801 hom., cov: 32)
• Consequence: CDKAL1 NM_017774.3 intron
• Clinical Significance: Uncertain significance no assertion criteria provided U:1
• Conservation: PhyloP100: -1.87

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=-1.06).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.557 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CDKAL1	NM_017774.3	c.371+30101A>G		intron_variant		ENST00000274695.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CDKAL1	ENST00000274695.8	c.371+30101A>G		intron_variant		1	NM_017774.3	P1
CDKAL1	ENST00000378610.1	c.371+30101A>G		intron_variant		2		P1

Frequencies

GnomAD3 genomes AF: 0.371 AC: 56381 AN: 151902 Hom.: 11781 Cov.: 32

Gnomad AFR AF: 0.563

Gnomad AMI AF: 0.363

Gnomad AMR AF: 0.311

Gnomad ASJ AF: 0.316

Gnomad EAS AF: 0.475

Gnomad SAS AF: 0.273

Gnomad FIN AF: 0.350

Gnomad MID AF: 0.310

Gnomad NFE AF: 0.274

Gnomad OTH AF: 0.346

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

GnomAD4 genome AF: 0.371 AC: 56440 AN: 152020 Hom.: 11801 Cov.: 32 AF XY: 0.374 AC XY: 27767 AN XY: 74316

Gnomad4 AFR AF: 0.563

Gnomad4 AMR AF: 0.310

Gnomad4 ASJ AF: 0.316

Gnomad4 EAS AF: 0.474

Gnomad4 SAS AF: 0.273

Gnomad4 FIN AF: 0.350

Gnomad4 NFE AF: 0.274

Gnomad4 OTH AF: 0.346

Alfa AF: 0.292 Hom.: 15719

Bravo AF: 0.379

Asia WGS AF: 0.351 AC: 1216 AN: 3472

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	-1.1
CADD	Benign	0.48
DANN	Benign	0.47

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: rs7756992; hg19: chr6-20679709;