ENST00000459970.1:n.67A>C

Variant names:

• chr6-36677811-A-C
• rs762624
• ENST00000459970.1:n.67A>C

Variant summary

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

The ENST00000459970.1(CDKN1A):​n.67A>C variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.3 in 1,222,592 control chromosomes in the GnomAD database, including 60,047 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 0.35 (10279 hom., cov: 31)
  • Exomes 𝑓: 0.29 (49768 hom.)
• Consequence: CDKN1A ENST00000459970.1 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.627
• Publications: 34 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]

DINOL (HGNC:53146): (damage induced long noncoding RNA)

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.58 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DINOL	NR_144384.1	n.749T>G		non_coding_transcript_exon_variant	Exon 1 of 1
CDKN1A	NM_001291549.3	c.-26A>C		5_prime_UTR_variant	Exon 2 of 4		NP_001278478.1
CDKN1A	NM_001374509.1	c.-26A>C		5_prime_UTR_variant	Exon 2 of 4		NP_001361438.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CDKN1A	ENST00000459970.1	n.67A>C		non_coding_transcript_exon_variant	Exon 2 of 3	5
DINOL	ENST00000643333.1	n.749T>G		non_coding_transcript_exon_variant	Exon 1 of 1
DINOL	ENST00000839528.1	n.444T>G		non_coding_transcript_exon_variant	Exon 2 of 2

Frequencies

GnomAD3 genomes AF: 0.353 AC: 53524 AN: 151810 Hom.: 10263 Cov.: 31

Gnomad AFR AF: 0.461

Gnomad AMI AF: 0.221

Gnomad AMR AF: 0.434

Gnomad ASJ AF: 0.330

Gnomad EAS AF: 0.598

Gnomad SAS AF: 0.412

Gnomad FIN AF: 0.237

Gnomad MID AF: 0.408

Gnomad NFE AF: 0.266

Gnomad OTH AF: 0.371

GnomAD2 exomes AF: 0.375 AC: 47723 AN: 127384 AF XY: 0.370

Gnomad AFR exome AF: 0.475

Gnomad AMR exome AF: 0.499

Gnomad ASJ exome AF: 0.334

Gnomad EAS exome AF: 0.593

Gnomad FIN exome AF: 0.230

Gnomad NFE exome AF: 0.270

Gnomad OTH exome AF: 0.338

GnomAD4 exome AF: 0.292 AC: 313157 AN: 1070664 Hom.: 49768 Cov.: 14 AF XY: 0.296 AC XY: 156704 AN XY: 530170

African (AFR) AF: 0.472 AC: 11805 AN: 24990

American (AMR) AF: 0.493 AC: 14962 AN: 30370

Ashkenazi Jewish (ASJ) AF: 0.331 AC: 6576 AN: 19860

East Asian (EAS) AF: 0.605 AC: 14102 AN: 23316

South Asian (SAS) AF: 0.391 AC: 28860 AN: 73864

European-Finnish (FIN) AF: 0.228 AC: 3087 AN: 13544

Middle Eastern (MID) AF: 0.358 AC: 1642 AN: 4588

European-Non Finnish (NFE) AF: 0.261 AC: 218357 AN: 837064

Other (OTH) AF: 0.320 AC: 13766 AN: 43068

GnomAD4 genome AF: 0.353 AC: 53575 AN: 151928 Hom.: 10279 Cov.: 31 AF XY: 0.354 AC XY: 26314 AN XY: 74248

African (AFR) AF: 0.460 AC: 19045 AN: 41386

American (AMR) AF: 0.435 AC: 6631 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.330 AC: 1143 AN: 3468

East Asian (EAS) AF: 0.598 AC: 3083 AN: 5156

South Asian (SAS) AF: 0.411 AC: 1972 AN: 4800

European-Finnish (FIN) AF: 0.237 AC: 2499 AN: 10562

Middle Eastern (MID) AF: 0.415 AC: 122 AN: 294

European-Non Finnish (NFE) AF: 0.266 AC: 18079 AN: 67978

Other (OTH) AF: 0.378 AC: 800 AN: 2114

Alfa AF: 0.301 Hom.: 14462

Bravo AF: 0.375

Asia WGS AF: 0.506 AC: 1758 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	10
DANN	Benign	0.79
PhyloP100		0.63
Mutation Taster		=300/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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: rs762624; hg19: chr6-36645588; COSMIC: COSV55187169; COSMIC: COSV55187169;