rs649392

chr11-69650025-G-Achr11-69650025-G-T

Variant summary

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

The NM_053056.3(CCND1):c.724-1093G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.514 in 152,038 control chromosomes in the GnomAD database, including 20,906 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 0.51 (20906 hom., cov: 33)
• Consequence: CCND1 NM_053056.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.69

Genes affected

CCND1 (HGNC:1582): (cyclin D1) The protein encoded by this gene belongs to the highly conserved cyclin family, whose members are characterized by a dramatic periodicity in protein abundance throughout the cell cycle. Cyclins function as regulators of CDK kinases. Different cyclins exhibit distinct expression and degradation patterns which contribute to the temporal coordination of each mitotic event. This cyclin forms a complex with and functions as a regulatory subunit of CDK4 or CDK6, whose activity is required for cell cycle G1/S transition. This protein has been shown to interact with tumor suppressor protein Rb and the expression of this gene is regulated positively by Rb. Mutations, amplification and overexpression of this gene, which alters cell cycle progression, are observed frequently in a variety of human cancers. [provided by RefSeq, Dec 2019]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.855 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CCND1	NM_053056.3	c.724-1093G>A		intron_variant		ENST00000227507.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CCND1	ENST00000227507.3	c.724-1093G>A		intron_variant		1	NM_053056.3	P1
CCND1	ENST00000542367.1	n.187-1093G>A		intron_variant, non_coding_transcript_variant		1

Frequencies

GnomAD3 genomes AF: 0.515 AC: 78200 AN: 151920 Hom.: 20909 Cov.: 33

Gnomad AFR AF: 0.386

Gnomad AMI AF: 0.607

Gnomad AMR AF: 0.485

Gnomad ASJ AF: 0.509

Gnomad EAS AF: 0.877

Gnomad SAS AF: 0.574

Gnomad FIN AF: 0.580

Gnomad MID AF: 0.506

Gnomad NFE AF: 0.556

Gnomad OTH AF: 0.534

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.514 AC: 78215 AN: 152038 Hom.: 20906 Cov.: 33 AF XY: 0.518 AC XY: 38526 AN XY: 74326

Gnomad4 AFR AF: 0.386

Gnomad4 AMR AF: 0.484

Gnomad4 ASJ AF: 0.509

Gnomad4 EAS AF: 0.877

Gnomad4 SAS AF: 0.576

Gnomad4 FIN AF: 0.580

Gnomad4 NFE AF: 0.556

Gnomad4 OTH AF: 0.534

Alfa AF: 0.546 Hom.: 31547

Bravo AF: 0.504

Asia WGS AF: 0.661 AC: 2298 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
Cadd	Benign	0.056
Dann	Benign	0.62

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: rs649392; hg19: chr11-69464793;