rs1465701

Variant names:

• chr19-10568166-T-C
• rs1465701
• NM_001800.4:c.141+347A>G

Variant summary

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

The NM_001800.4(CDKN2D):​c.141+347A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.697 in 151,718 control chromosomes in the GnomAD database, including 37,655 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 0.70 (37655 hom., cov: 29)
• Consequence: CDKN2D NM_001800.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.14
• Publications: 30 publications found

Genes affected

CDKN2D (HGNC:1790): (cyclin dependent kinase inhibitor 2D) The protein encoded by this gene is a member of the INK4 family of cyclin-dependent kinase inhibitors. This protein has been shown to form a stable complex with CDK4 or CDK6, and prevent the activation of the CDK kinases, thus function as a cell growth regulator that controls cell cycle G1 progression. The abundance of the transcript of this gene was found to oscillate in a cell-cycle dependent manner with the lowest expression at mid G1 and a maximal expression during S phase. The negative regulation of the cell cycle involved in this protein was shown to participate in repressing neuronal proliferation, as well as spermatogenesis. Two alternatively spliced variants of this gene, which encode an identical protein, have been reported. [provided by RefSeq, Jul 2008]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.74).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.752 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CDKN2D	NM_001800.4	c.141+347A>G		intron_variant	Intron 1 of 1	ENST00000393599.3	NP_001791.1
CDKN2D	NM_079421.3	c.141+347A>G		intron_variant	Intron 2 of 2		NP_524145.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CDKN2D	ENST00000393599.3	c.141+347A>G		intron_variant	Intron 1 of 1	1	NM_001800.4	ENSP00000377224.1
CDKN2D	ENST00000335766.2	c.141+347A>G		intron_variant	Intron 2 of 2	1		ENSP00000337056.1

Frequencies

GnomAD3 genomes AF: 0.697 AC: 105654 AN: 151600 Hom.: 37632 Cov.: 29

Gnomad AFR AF: 0.700

Gnomad AMI AF: 0.901

Gnomad AMR AF: 0.548

Gnomad ASJ AF: 0.600

Gnomad EAS AF: 0.319

Gnomad SAS AF: 0.582

Gnomad FIN AF: 0.761

Gnomad MID AF: 0.694

Gnomad NFE AF: 0.758

Gnomad OTH AF: 0.689

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

GnomAD4 genome AF: 0.697 AC: 105731 AN: 151718 Hom.: 37655 Cov.: 29 AF XY: 0.689 AC XY: 51064 AN XY: 74144

African (AFR) AF: 0.700 AC: 28929 AN: 41340

American (AMR) AF: 0.547 AC: 8326 AN: 15214

Ashkenazi Jewish (ASJ) AF: 0.600 AC: 2082 AN: 3468

East Asian (EAS) AF: 0.320 AC: 1638 AN: 5126

South Asian (SAS) AF: 0.583 AC: 2795 AN: 4796

European-Finnish (FIN) AF: 0.761 AC: 8021 AN: 10546

Middle Eastern (MID) AF: 0.695 AC: 203 AN: 292

European-Non Finnish (NFE) AF: 0.758 AC: 51456 AN: 67916

Other (OTH) AF: 0.692 AC: 1459 AN: 2108

Alfa AF: 0.727 Hom.: 78697

Bravo AF: 0.681

Asia WGS AF: 0.495 AC: 1724 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.74
CADD	Benign	0.75
DANN	Benign	0.77
PhyloP100		-2.1
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: rs1465701; hg19: chr19-10678842;