rs4510656

Variant names:

• chr6-20766466-C-A
• rs4510656
• NM_017774.3:c.517+7823C>A

Your query was ambiguous. Multiple possible variants found:

• chr6-20766466-C-A
• chr6-20766466-C-G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 21 publications found

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]

ENSG00000233848 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
CDKAL1	NM_017774.3	c.517+7823C>A		intron_variant	Intron 7 of 15	ENST00000274695.8	NP_060244.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CDKAL1	ENST00000274695.8	c.517+7823C>A		intron_variant	Intron 7 of 15	1	NM_017774.3	ENSP00000274695.4
CDKAL1	ENST00000378610.1	c.517+7823C>A		intron_variant	Intron 5 of 13	2		ENSP00000367873.1
ENSG00000233848	ENST00000421167.1	n.398+6370G>T		intron_variant	Intron 3 of 4	3

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

African (AFR) AF: 0.363 AC: 15047 AN: 41434

American (AMR) AF: 0.383 AC: 5851 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.398 AC: 1380 AN: 3464

East Asian (EAS) AF: 0.196 AC: 1014 AN: 5168

South Asian (SAS) AF: 0.260 AC: 1255 AN: 4822

European-Finnish (FIN) AF: 0.372 AC: 3931 AN: 10568

Middle Eastern (MID) AF: 0.408 AC: 119 AN: 292

European-Non Finnish (NFE) AF: 0.433 AC: 29431 AN: 67908

Other (OTH) AF: 0.406 AC: 855 AN: 2106

Alfa AF: 0.393 Hom.: 5929

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
PhyloP100		0.0070
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs4510656; hg19: chr6-20766697;