rs7738382

chr6-20746005-C-A

Variant summary

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

The NM_017774.3(CDKAL1):c.468+6390C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.642 in 152,016 control chromosomes in the GnomAD database, including 32,087 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 0.64 (32087 hom., cov: 32)
• Consequence: CDKAL1 NM_017774.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.38

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=-1.01).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.722 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CDKAL1	NM_017774.3	c.468+6390C>A		intron_variant		ENST00000274695.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CDKAL1	ENST00000274695.8	c.468+6390C>A		intron_variant		1	NM_017774.3	P1
CDKAL1	ENST00000378610.1	c.468+6390C>A		intron_variant		2		P1

Frequencies

GnomAD3 genomes AF: 0.642 AC: 97476 AN: 151896 Hom.: 32080 Cov.: 32

Gnomad AFR AF: 0.483

Gnomad AMI AF: 0.938

Gnomad AMR AF: 0.659

Gnomad ASJ AF: 0.716

Gnomad EAS AF: 0.532

Gnomad SAS AF: 0.598

Gnomad FIN AF: 0.711

Gnomad MID AF: 0.650

Gnomad NFE AF: 0.727

Gnomad OTH AF: 0.650

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

GnomAD4 genome AF: 0.642 AC: 97527 AN: 152016 Hom.: 32087 Cov.: 32 AF XY: 0.640 AC XY: 47530 AN XY: 74310

Gnomad4 AFR AF: 0.482

Gnomad4 AMR AF: 0.658

Gnomad4 ASJ AF: 0.716

Gnomad4 EAS AF: 0.533

Gnomad4 SAS AF: 0.599

Gnomad4 FIN AF: 0.711

Gnomad4 NFE AF: 0.727

Gnomad4 OTH AF: 0.648

Alfa AF: 0.701 Hom.: 50331

Bravo AF: 0.632

Asia WGS AF: 0.553 AC: 1928 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
Cadd	Benign	0.048
Dann	Benign	0.23
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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: rs7738382; hg19: chr6-20746236;