rs4712523

chr6-20657333-A-Gchr6-20657333-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+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

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=-0.84).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.596 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CDKAL1	NM_017774.3	c.371+7956A>G		intron_variant		ENST00000274695.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CDKAL1	ENST00000274695.8	c.371+7956A>G		intron_variant		1	NM_017774.3	P1
CDKAL1	ENST00000378610.1	c.371+7956A>G		intron_variant		2		P1

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

Gnomad4 AFR AF: 0.602

Gnomad4 AMR AF: 0.329

Gnomad4 ASJ AF: 0.348

Gnomad4 EAS AF: 0.401

Gnomad4 SAS AF: 0.287

Gnomad4 FIN AF: 0.373

Gnomad4 NFE AF: 0.316

Gnomad4 OTH AF: 0.377

Alfa AF: 0.328 Hom.: 18378

Bravo AF: 0.408

Asia WGS AF: 0.353 AC: 1225 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
Cadd	Benign	0.036
Dann	Benign	0.53

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: rs4712523; hg19: chr6-20657564;