rs730506

Positions:

• chr6-36678191-G-C

Variant summary

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

The NR_144384.1(DINOL):​n.369C>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 0.211 in 335,600 control chromosomes in the GnomAD database, including 7,895 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 0.22 (3672 hom., cov: 32)
  • Exomes 𝑓: 0.21 (4223 hom.)
• Consequence: DINOL NR_144384.1 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.316

Genes affected

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

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=-0.82).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.287 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DINOL	NR_144384.1	n.369C>G		non_coding_transcript_exon_variant	1/1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DINOL	ENST00000643333.1	n.369C>G		non_coding_transcript_exon_variant	1/1
CDKN1A	ENST00000448526.6	c.-6+258G>C		intron_variant		3		ENSP00000409259	P1
CDKN1A	ENST00000615513.4	c.-6+1667G>C		intron_variant		2		ENSP00000482768	P1
CDKN1A	ENST00000459970.1	n.189+258G>C		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.218 AC: 33123 AN: 152018 Hom.: 3663 Cov.: 32

Gnomad AFR AF: 0.260

Gnomad AMI AF: 0.0669

Gnomad AMR AF: 0.199

Gnomad ASJ AF: 0.264

Gnomad EAS AF: 0.129

Gnomad SAS AF: 0.299

Gnomad FIN AF: 0.179

Gnomad MID AF: 0.299

Gnomad NFE AF: 0.202

Gnomad OTH AF: 0.252

GnomAD4 exome AF: 0.206 AC: 37815 AN: 183464 Hom.: 4223 Cov.: 0 AF XY: 0.217 AC XY: 21705 AN XY: 100098

Gnomad4 AFR exome AF: 0.253

Gnomad4 AMR exome AF: 0.154

Gnomad4 ASJ exome AF: 0.257

Gnomad4 EAS exome AF: 0.112

Gnomad4 SAS exome AF: 0.278

Gnomad4 FIN exome AF: 0.164

Gnomad4 NFE exome AF: 0.191

Gnomad4 OTH exome AF: 0.214

GnomAD4 genome AF: 0.218 AC: 33146 AN: 152136 Hom.: 3672 Cov.: 32 AF XY: 0.217 AC XY: 16107 AN XY: 74362

Gnomad4 AFR AF: 0.260

Gnomad4 AMR AF: 0.198

Gnomad4 ASJ AF: 0.264

Gnomad4 EAS AF: 0.129

Gnomad4 SAS AF: 0.300

Gnomad4 FIN AF: 0.179

Gnomad4 NFE AF: 0.202

Gnomad4 OTH AF: 0.259

Alfa AF: 0.208 Hom.: 404

Bravo AF: 0.218

Asia WGS AF: 0.261 AC: 909 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	7.1
DANN	Benign	0.72

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: rs730506; hg19: chr6-36645968;