6-36679748-C-T

Variant names:

• chr6-36679748-C-T
• rs3176331
• NM_000389.5:c.-6+950C>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+950C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.141 in 152,112 control chromosomes in the GnomAD database, including 1,607 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 0.14 (1607 hom., cov: 30)
• Consequence: CDKN1A NM_000389.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.555
• Publications: 9 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=-0.81).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.165 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CDKN1A	NM_000389.5	c.-6+950C>T		intron_variant	Intron 1 of 2	ENST00000244741.10	NP_000380.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CDKN1A	ENST00000244741.10	c.-6+950C>T		intron_variant	Intron 1 of 2	1	NM_000389.5	ENSP00000244741.6

Frequencies

GnomAD3 genomes AF: 0.141 AC: 21446 AN: 151994 Hom.: 1606 Cov.: 30

Gnomad AFR AF: 0.168

Gnomad AMI AF: 0.109

Gnomad AMR AF: 0.117

Gnomad ASJ AF: 0.214

Gnomad EAS AF: 0.107

Gnomad SAS AF: 0.0530

Gnomad FIN AF: 0.148

Gnomad MID AF: 0.130

Gnomad NFE AF: 0.134

Gnomad OTH AF: 0.142

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

GnomAD4 genome AF: 0.141 AC: 21459 AN: 152112 Hom.: 1607 Cov.: 30 AF XY: 0.141 AC XY: 10514 AN XY: 74360

African (AFR) AF: 0.168 AC: 6973 AN: 41498

American (AMR) AF: 0.117 AC: 1794 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.214 AC: 743 AN: 3470

East Asian (EAS) AF: 0.107 AC: 552 AN: 5156

South Asian (SAS) AF: 0.0528 AC: 255 AN: 4830

European-Finnish (FIN) AF: 0.148 AC: 1573 AN: 10602

Middle Eastern (MID) AF: 0.126 AC: 37 AN: 294

European-Non Finnish (NFE) AF: 0.134 AC: 9136 AN: 67938

Other (OTH) AF: 0.141 AC: 297 AN: 2110

Alfa AF: 0.133 Hom.: 2024

Bravo AF: 0.142

Asia WGS AF: 0.0750 AC: 261 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	8.6
DANN	Benign	0.92
PhyloP100		0.56
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: rs3176331; hg19: chr6-36647525;