11-69651969-C-G

Variant names:

• chr11-69651969-C-G
• rs678653
• NM_053056.3:c.*687C>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 59 publications found

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]

CCND1 Gene-Disease associations (from GenCC):

• von Hippel-Lindau disease

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
CCND1	NM_053056.3	c.*687C>G		3_prime_UTR_variant	Exon 5 of 5	ENST00000227507.3	NP_444284.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CCND1	ENST00000227507.3	c.*687C>G		3_prime_UTR_variant	Exon 5 of 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

African (AFR) AF: 0.240 AC: 933 AN: 3886

American (AMR) AF: 0.475 AC: 1182 AN: 2490

Ashkenazi Jewish (ASJ) AF: 0.549 AC: 2801 AN: 5106

East Asian (EAS) AF: 0.878 AC: 10004 AN: 11388

South Asian (SAS) AF: 0.605 AC: 422 AN: 698

European-Finnish (FIN) AF: 0.786 AC: 55 AN: 70

Middle Eastern (MID) AF: 0.588 AC: 288 AN: 490

European-Non Finnish (NFE) AF: 0.633 AC: 31589 AN: 49866

Other (OTH) AF: 0.589 AC: 3982 AN: 6760

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

African (AFR) AF: 0.230 AC: 9524 AN: 41432

American (AMR) AF: 0.493 AC: 7527 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.559 AC: 1938 AN: 3470

East Asian (EAS) AF: 0.876 AC: 4501 AN: 5136

South Asian (SAS) AF: 0.599 AC: 2872 AN: 4798

European-Finnish (FIN) AF: 0.753 AC: 7947 AN: 10554

Middle Eastern (MID) AF: 0.510 AC: 150 AN: 294

European-Non Finnish (NFE) AF: 0.642 AC: 43610 AN: 67942

Other (OTH) AF: 0.548 AC: 1155 AN: 2106

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
PhyloP100		2.3
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs678653; hg19: chr11-69466737;