rs4510656

chr6-20766466-C-Achr6-20766466-C-G

Variant summary

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

The NM_017774.3(CDKAL1):c.517+7823C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.39 in 151,944 control chromosomes in the GnomAD database, including 11,824 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 0.39 (11824 hom., cov: 32)
• Consequence: CDKAL1 NM_017774.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.00700

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]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.429 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CDKAL1	NM_017774.3	c.517+7823C>A		intron_variant		ENST00000274695.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CDKAL1	ENST00000274695.8	c.517+7823C>A		intron_variant		1	NM_017774.3	P1
	ENST00000421167.1	n.398+6370G>T		intron_variant, non_coding_transcript_variant		3
CDKAL1	ENST00000378610.1	c.517+7823C>A		intron_variant		2		P1

Frequencies

GnomAD3 genomes AF: 0.390 AC: 59246 AN: 151826 Hom.: 11821 Cov.: 32

Gnomad AFR AF: 0.363

Gnomad AMI AF: 0.429

Gnomad AMR AF: 0.384

Gnomad ASJ AF: 0.398

Gnomad EAS AF: 0.195

Gnomad SAS AF: 0.261

Gnomad FIN AF: 0.372

Gnomad MID AF: 0.398

Gnomad NFE AF: 0.433

Gnomad OTH AF: 0.410

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

GnomAD4 genome AF: 0.390 AC: 59273 AN: 151944 Hom.: 11824 Cov.: 32 AF XY: 0.383 AC XY: 28443 AN XY: 74278

Gnomad4 AFR AF: 0.363

Gnomad4 AMR AF: 0.383

Gnomad4 ASJ AF: 0.398

Gnomad4 EAS AF: 0.196

Gnomad4 SAS AF: 0.260

Gnomad4 FIN AF: 0.372

Gnomad4 NFE AF: 0.433

Gnomad4 OTH AF: 0.406

Alfa AF: 0.388 Hom.: 5159

Bravo AF: 0.393

Asia WGS AF: 0.212 AC: 741 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
Cadd	Benign	1.6
Dann	Benign	0.38

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: rs4510656; hg19: chr6-20766697;