rs9356754

Variant names:

• chr6-20808511-G-T
• rs9356754
• NM_017774.3:c.638+27246G>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.638+27246G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.51 in 151,924 control chromosomes in the GnomAD database, including 20,172 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 0.51 (20172 hom., cov: 31)
• Consequence: CDKAL1 NM_017774.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.798
• Publications: 5 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=-0.77).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.54 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CDKAL1	NM_017774.3	c.638+27246G>T		intron_variant	Intron 8 of 15	ENST00000274695.8	NP_060244.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CDKAL1	ENST00000274695.8	c.638+27246G>T		intron_variant	Intron 8 of 15	1	NM_017774.3	ENSP00000274695.4
CDKAL1	ENST00000378610.1	c.638+27246G>T		intron_variant	Intron 6 of 13	2		ENSP00000367873.1

Frequencies

GnomAD3 genomes AF: 0.510 AC: 77458 AN: 151806 Hom.: 20154 Cov.: 31

Gnomad AFR AF: 0.449

Gnomad AMI AF: 0.762

Gnomad AMR AF: 0.468

Gnomad ASJ AF: 0.585

Gnomad EAS AF: 0.375

Gnomad SAS AF: 0.432

Gnomad FIN AF: 0.653

Gnomad MID AF: 0.434

Gnomad NFE AF: 0.544

Gnomad OTH AF: 0.488

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

GnomAD4 genome AF: 0.510 AC: 77535 AN: 151924 Hom.: 20172 Cov.: 31 AF XY: 0.513 AC XY: 38106 AN XY: 74260

African (AFR) AF: 0.449 AC: 18616 AN: 41424

American (AMR) AF: 0.468 AC: 7147 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.585 AC: 2030 AN: 3470

East Asian (EAS) AF: 0.375 AC: 1935 AN: 5160

South Asian (SAS) AF: 0.433 AC: 2086 AN: 4816

European-Finnish (FIN) AF: 0.653 AC: 6883 AN: 10544

Middle Eastern (MID) AF: 0.442 AC: 130 AN: 294

European-Non Finnish (NFE) AF: 0.544 AC: 36983 AN: 67928

Other (OTH) AF: 0.489 AC: 1030 AN: 2108

Alfa AF: 0.526 Hom.: 13239

Bravo AF: 0.493

Asia WGS AF: 0.426 AC: 1486 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
CADD	Benign	3.4
DANN	Benign	0.70
PhyloP100		0.80
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: rs9356754; hg19: chr6-20808742;