ENST00000459970.1:n.67A>G

Variant names:

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

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The ENST00000459970.1(CDKN1A):​n.67A>G variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 31)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DINOL	NR_144384.1	n.749T>C		non_coding_transcript_exon_variant	Exon 1 of 1
CDKN1A	NM_001291549.3	c.-26A>G		5_prime_UTR_variant	Exon 2 of 4		NP_001278478.1
CDKN1A	NM_001374509.1	c.-26A>G		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>G		non_coding_transcript_exon_variant	Exon 2 of 3	5
DINOL	ENST00000643333.1	n.749T>C		non_coding_transcript_exon_variant	Exon 1 of 1
DINOL	ENST00000839528.1	n.444T>C		non_coding_transcript_exon_variant	Exon 2 of 2

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1073156 Hom.: 0 Cov.: 14 AF XY: 0.00 AC XY: 0 AN XY: 531338

African (AFR) AF: 0.00 AC: 0 AN: 25050

American (AMR) AF: 0.00 AC: 0 AN: 30400

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19892

East Asian (EAS) AF: 0.00 AC: 0 AN: 23380

South Asian (SAS) AF: 0.00 AC: 0 AN: 73958

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 13560

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4604

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 839142

Other (OTH) AF: 0.00 AC: 0 AN: 43170

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	10
DANN	Benign	0.78
PhyloP100		0.63

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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;