rs3176337

chr6-36681143-A-Cchr6-36681143-A-Gchr6-36681143-A-T

Variant summary

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

The NM_000389.5(CDKN1A):c.-6+2345A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.643 in 152,012 control chromosomes in the GnomAD database, including 32,523 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 (32523 hom., cov: 31)
• Consequence: CDKN1A NM_000389.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.121

Genes affected

CDKN1A (HGNC:1784): (cyclin dependent kinase inhibitor 1A) This gene encodes a potent cyclin-dependent kinase inhibitor. The encoded protein binds to and inhibits the activity of cyclin-cyclin-dependent kinase2 or -cyclin-dependent kinase4 complexes, and thus functions as a regulator of cell cycle progression at G1. The expression of this gene is tightly controlled by the tumor suppressor protein p53, through which this protein mediates the p53-dependent cell cycle G1 phase arrest in response to a variety of stress stimuli. This protein can interact with proliferating cell nuclear antigen, a DNA polymerase accessory factor, and plays a regulatory role in S phase DNA replication and DNA damage repair. This protein was reported to be specifically cleaved by CASP3-like caspases, which thus leads to a dramatic activation of cyclin-dependent kinase2, and may be instrumental in the execution of apoptosis following caspase activation. Mice that lack this gene have the ability to regenerate damaged or missing tissue. Multiple alternatively spliced variants have been found for this gene. [provided by RefSeq, Sep 2015]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.803 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CDKN1A	NM_000389.5	c.-6+2345A>C		intron_variant		ENST00000244741.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CDKN1A	ENST00000244741.10	c.-6+2345A>C		intron_variant		1	NM_000389.5	P1

Frequencies

GnomAD3 genomes AF: 0.643 AC: 97649 AN: 151892 Hom.: 32463 Cov.: 31

Gnomad AFR AF: 0.810

Gnomad AMI AF: 0.460

Gnomad AMR AF: 0.680

Gnomad ASJ AF: 0.634

Gnomad EAS AF: 0.755

Gnomad SAS AF: 0.650

Gnomad FIN AF: 0.525

Gnomad MID AF: 0.668

Gnomad NFE AF: 0.545

Gnomad OTH AF: 0.665

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

GnomAD4 genome AF: 0.643 AC: 97773 AN: 152012 Hom.: 32523 Cov.: 31 AF XY: 0.645 AC XY: 47900 AN XY: 74300

Gnomad4 AFR AF: 0.810

Gnomad4 AMR AF: 0.680

Gnomad4 ASJ AF: 0.634

Gnomad4 EAS AF: 0.755

Gnomad4 SAS AF: 0.649

Gnomad4 FIN AF: 0.525

Gnomad4 NFE AF: 0.544

Gnomad4 OTH AF: 0.670

Alfa AF: 0.596 Hom.: 7078

Bravo AF: 0.664

Asia WGS AF: 0.721 AC: 2501 AN: 3468

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
Cadd	Benign	6.7
Dann	Benign	0.46

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: rs3176337; hg19: chr6-36648920;