Variant 6-36677811-A-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NR_144384.1(DINOL):n.749T>G 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

DINOL
NR_144384.1 non_coding_transcript_exon

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.627

Variant links:

Genes affected

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

DINOL links:

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]

CDKN1A links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -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/exons	MANE	Protein	UniProt
DINOL	NR_144384.1 linkuse as main transcript	n.749T>G		non_coding_transcript_exon_variant	1/1

Ensembl

Gene	Transcript	HGVSc	Effect	#exon/exons	TSL	Protein	Appris
DINOL	ENST00000643333.1 linkuse as main transcript	n.749T>G	non_coding_transcript_exon_variant	1/1
CDKN1A	ENST00000448526.6 linkuse as main transcript	c.-37-91A>C	intron_variant		3	ENSP00000409259	P1
CDKN1A	ENST00000615513.4 linkuse as main transcript	c.-6+1287A>C	intron_variant		2	ENSP00000482768	P1
CDKN1A	ENST00000459970.1 linkuse as main transcript	n.67A>C	non_coding_transcript_exon_variant	2/3	5

Frequencies

GnomAD3 genomes

AF:

0.353

AC:

53524

AN:

151810

Hom.:

10263

Cov.:

show subpopulations

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

GnomAD3 exomes

AF:

0.375

AC:

47723

AN:

127384

Hom.:

9866

AF XY:

0.370

AC XY:

25795

AN XY:

69716

show subpopulations

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 SAS exome

AF:

0.388

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.:

AF XY:

0.296

AC XY:

156704

AN XY:

530170

show subpopulations

Gnomad4 AFR exome

AF:

0.472

Gnomad4 AMR exome

AF:

0.493

Gnomad4 ASJ exome

AF:

0.331

Gnomad4 EAS exome

AF:

0.605

Gnomad4 SAS exome

AF:

0.391

Gnomad4 FIN exome

AF:

0.228

Gnomad4 NFE exome

AF:

0.261

Gnomad4 OTH exome

AF:

0.320

GnomAD4 genome

AF:

0.353

AC:

53575

AN:

151928

Hom.:

10279

Cov.:

AF XY:

0.354

AC XY:

26314

AN XY:

74248

show subpopulations

Gnomad4 AFR

AF:

0.460

Gnomad4 AMR

AF:

0.435

Gnomad4 ASJ

AF:

0.330

Gnomad4 EAS

AF:

0.598

Gnomad4 SAS

AF:

0.411

Gnomad4 FIN

AF:

0.237

Gnomad4 NFE

AF:

0.266

Gnomad4 OTH

AF:

0.378

Alfa

AF:

0.269

Hom.:

2465

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

DANN

Benign

0.79

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over