11-69651969-C-G

Position:

• chr11-69651969-C-G

Variant summary

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

The NM_053056.3(CCND1):​c.*687C>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.563 in 232,662 control chromosomes in the GnomAD database, including 40,956 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 0.53 (23939 hom., cov: 31)
  • Exomes 𝑓: 0.63 (17017 hom.)
• Consequence: CCND1 NM_053056.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.33

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=-0.82).
• 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	Protein	UniProt
CCND1	NM_053056.3	c.*687C>G		3_prime_UTR_variant	5/5	ENST00000227507.3	NP_444284.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CCND1	ENST00000227507.3	c.*687C>G		3_prime_UTR_variant	5/5	1	NM_053056.3	ENSP00000227507.2

Frequencies

GnomAD3 genomes AF: 0.526 AC: 79823 AN: 151790 Hom.: 23945 Cov.: 31

Gnomad AFR AF: 0.230

Gnomad AMI AF: 0.662

Gnomad AMR AF: 0.494

Gnomad ASJ AF: 0.559

Gnomad EAS AF: 0.876

Gnomad SAS AF: 0.597

Gnomad FIN AF: 0.753

Gnomad MID AF: 0.516

Gnomad NFE AF: 0.642

Gnomad OTH AF: 0.547

GnomAD4 exome AF: 0.635 AC: 51256 AN: 80754 Hom.: 17017 Cov.: 0 AF XY: 0.636 AC XY: 23597 AN XY: 37112

Gnomad4 AFR exome AF: 0.240

Gnomad4 AMR exome AF: 0.475

Gnomad4 ASJ exome AF: 0.549

Gnomad4 EAS exome AF: 0.878

Gnomad4 SAS exome AF: 0.605

Gnomad4 FIN exome AF: 0.786

Gnomad4 NFE exome AF: 0.633

Gnomad4 OTH exome AF: 0.589

GnomAD4 genome AF: 0.526 AC: 79828 AN: 151908 Hom.: 23939 Cov.: 31 AF XY: 0.532 AC XY: 39510 AN XY: 74230

Gnomad4 AFR AF: 0.230

Gnomad4 AMR AF: 0.493

Gnomad4 ASJ AF: 0.559

Gnomad4 EAS AF: 0.876

Gnomad4 SAS AF: 0.599

Gnomad4 FIN AF: 0.753

Gnomad4 NFE AF: 0.642

Gnomad4 OTH AF: 0.548

Alfa AF: 0.570 Hom.: 3220

Bravo AF: 0.495

Asia WGS AF: 0.668 AC: 2320 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	2.6
DANN	Benign	0.67

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: rs678653; hg19: chr11-69466737;