rs4712523

Variant names:

• chr6-20657333-A-G
• rs4712523
• NM_017774.3:c.371+7956A>G

Your query was ambiguous. Multiple possible variants found:

• chr6-20657333-A-G
• chr6-20657333-A-T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_017774.3(CDKAL1):​c.371+7956A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.403 in 151,950 control chromosomes in the GnomAD database, including 13,587 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 0.40 (13587 hom., cov: 31)
• Consequence: CDKAL1 NM_017774.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.48
• Publications: 87 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]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.596 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_017774.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CDKAL1	NM_017774.3	MANE Select	c.371+7956A>G		intron	N/A	NP_060244.2	Q5VV42-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CDKAL1	ENST00000274695.8	TSL:1 MANE Select	c.371+7956A>G		intron	N/A	ENSP00000274695.4	Q5VV42-1
	CDKAL1	ENST00000946780.1		c.371+7956A>G		intron	N/A	ENSP00000616839.1
	CDKAL1	ENST00000378610.1	TSL:2	c.371+7956A>G		intron	N/A	ENSP00000367873.1	Q5VV42-1

Frequencies

GnomAD3 genomes AF: 0.403 AC: 61208 AN: 151832 Hom.: 13580 Cov.: 31

Gnomad AFR AF: 0.602

Gnomad AMI AF: 0.378

Gnomad AMR AF: 0.329

Gnomad ASJ AF: 0.348

Gnomad EAS AF: 0.401

Gnomad SAS AF: 0.288

Gnomad FIN AF: 0.373

Gnomad MID AF: 0.339

Gnomad NFE AF: 0.316

Gnomad OTH AF: 0.378

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

GnomAD4 genome AF: 0.403 AC: 61243 AN: 151950 Hom.: 13587 Cov.: 31 AF XY: 0.402 AC XY: 29877 AN XY: 74268

African (AFR) AF: 0.602 AC: 24915 AN: 41398

American (AMR) AF: 0.329 AC: 5016 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.348 AC: 1207 AN: 3468

East Asian (EAS) AF: 0.401 AC: 2070 AN: 5162

South Asian (SAS) AF: 0.287 AC: 1383 AN: 4818

European-Finnish (FIN) AF: 0.373 AC: 3946 AN: 10566

Middle Eastern (MID) AF: 0.337 AC: 99 AN: 294

European-Non Finnish (NFE) AF: 0.316 AC: 21468 AN: 67964

Other (OTH) AF: 0.377 AC: 795 AN: 2106

Alfa AF: 0.342 Hom.: 41281

Bravo AF: 0.408

Asia WGS AF: 0.353 AC: 1225 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	0.036
DANN	Benign	0.53
PhyloP100		-1.5
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: rs4712523; hg19: chr6-20657564;