6-36686965-G-A

Position:

• chr6-36686965-G-A

Variant summary

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

The NM_000389.5(CDKN1A):​c.*1165G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.013 in 233,770 control chromosomes in the GnomAD database, including 64 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 0.017 (60 hom., cov: 32)
  • Exomes 𝑓: 0.0058 (4 hom.)
• Consequence: CDKN1A NM_000389.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.484

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=-0.54).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0512 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CDKN1A	NM_000389.5	c.*1165G>A		3_prime_UTR_variant	3/3	ENST00000244741.10	NP_000380.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CDKN1A	ENST00000244741.10	c.*1165G>A		3_prime_UTR_variant	3/3	1	NM_000389.5	ENSP00000244741	P1
CDKN1A	ENST00000405375.5	c.*1165G>A		3_prime_UTR_variant	3/3	1		ENSP00000384849	P1
CDKN1A	ENST00000448526.6	c.*1165G>A		3_prime_UTR_variant	4/4	3		ENSP00000409259	P1
CDKN1A	ENST00000615513.4	c.*1165G>A		3_prime_UTR_variant	3/3	2		ENSP00000482768	P1

Frequencies

GnomAD3 genomes AF: 0.0168 AC: 2556 AN: 152162 Hom.: 59 Cov.: 32

Gnomad AFR AF: 0.0530

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0120

Gnomad ASJ AF: 0.000288

Gnomad EAS AF: 0.00615

Gnomad SAS AF: 0.000415

Gnomad FIN AF: 0.000189

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.00163

Gnomad OTH AF: 0.0129

GnomAD4 exome AF: 0.00584 AC: 476 AN: 81490 Hom.: 4 Cov.: 0 AF XY: 0.00581 AC XY: 218 AN XY: 37540

Gnomad4 AFR exome AF: 0.0536

Gnomad4 AMR exome AF: 0.00520

Gnomad4 ASJ exome AF: 0.000975

Gnomad4 EAS exome AF: 0.0117

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00140

Gnomad4 OTH exome AF: 0.00664

GnomAD4 genome AF: 0.0168 AC: 2561 AN: 152280 Hom.: 60 Cov.: 32 AF XY: 0.0164 AC XY: 1221 AN XY: 74452

Gnomad4 AFR AF: 0.0530

Gnomad4 AMR AF: 0.0120

Gnomad4 ASJ AF: 0.000288

Gnomad4 EAS AF: 0.00617

Gnomad4 SAS AF: 0.000207

Gnomad4 FIN AF: 0.000189

Gnomad4 NFE AF: 0.00163

Gnomad4 OTH AF: 0.0128

Alfa AF: 0.00502 Hom.: 12

Bravo AF: 0.0189

Asia WGS AF: 0.00751 AC: 26 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.54
CADD	Benign	9.7
DANN	Benign	0.77
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0

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: rs3176359; hg19: chr6-36654742;