rs3176337

Variant names:

• chr6-36681143-A-C
• rs3176337
• NM_000389.5:c.-6+2345A>C

Your query was ambiguous. Multiple possible variants found:

• chr6-36681143-A-C
• chr6-36681143-A-G
• chr6-36681143-A-T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 6 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000389.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CDKN1A	NM_000389.5	MANE Select	c.-6+2345A>C		intron	N/A	NP_000380.1
	CDKN1A	NM_001291549.3		c.98-2954A>C		intron	N/A	NP_001278478.1
	CDKN1A	NM_001374509.1		c.98-2954A>C		intron	N/A	NP_001361438.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CDKN1A	ENST00000244741.10	TSL:1 MANE Select	c.-6+2345A>C		intron	N/A	ENSP00000244741.6
	CDKN1A	ENST00000405375.5	TSL:1	c.-6+2204A>C		intron	N/A	ENSP00000384849.1
	CDKN1A	ENST00000373711.4	TSL:5	c.-96-1497A>C		intron	N/A	ENSP00000362815.1

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

African (AFR) AF: 0.810 AC: 33601 AN: 41468

American (AMR) AF: 0.680 AC: 10393 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.634 AC: 2197 AN: 3468

East Asian (EAS) AF: 0.755 AC: 3894 AN: 5158

South Asian (SAS) AF: 0.649 AC: 3122 AN: 4814

European-Finnish (FIN) AF: 0.525 AC: 5545 AN: 10568

Middle Eastern (MID) AF: 0.673 AC: 198 AN: 294

European-Non Finnish (NFE) AF: 0.544 AC: 36991 AN: 67938

Other (OTH) AF: 0.670 AC: 1414 AN: 2112

Alfa AF: 0.586 Hom.: 15838

Bravo AF: 0.664

Asia WGS AF: 0.721 AC: 2501 AN: 3468

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	6.7
DANN	Benign	0.46
PhyloP100		0.12
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: rs3176337; hg19: chr6-36648920;