rs647451

Variant names:

• chr11-69646963-C-T
• rs647451
• NM_053056.3:c.575-1031C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_053056.3(CCND1):​c.575-1031C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.421 in 152,028 control chromosomes in the GnomAD database, including 14,757 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 0.42 (14757 hom., cov: 33)
• Consequence: CCND1 NM_053056.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.13
• Publications: 6 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=-0.88).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.802 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CCND1	NM_053056.3	c.575-1031C>T		intron_variant	Intron 3 of 4	ENST00000227507.3	NP_444284.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CCND1	ENST00000227507.3	c.575-1031C>T		intron_variant	Intron 3 of 4	1	NM_053056.3	ENSP00000227507.2
CCND1	ENST00000536559.1	c.199-1031C>T		intron_variant	Intron 1 of 1	3		ENSP00000438482.1
CCND1	ENST00000545484.1	n.281-1031C>T		intron_variant	Intron 1 of 1	5

Frequencies

GnomAD3 genomes AF: 0.422 AC: 64040 AN: 151910 Hom.: 14764 Cov.: 33

Gnomad AFR AF: 0.246

Gnomad AMI AF: 0.411

Gnomad AMR AF: 0.415

Gnomad ASJ AF: 0.450

Gnomad EAS AF: 0.823

Gnomad SAS AF: 0.559

Gnomad FIN AF: 0.507

Gnomad MID AF: 0.487

Gnomad NFE AF: 0.474

Gnomad OTH AF: 0.450

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

GnomAD4 genome AF: 0.421 AC: 64048 AN: 152028 Hom.: 14757 Cov.: 33 AF XY: 0.428 AC XY: 31807 AN XY: 74300

African (AFR) AF: 0.246 AC: 10211 AN: 41490

American (AMR) AF: 0.415 AC: 6337 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.450 AC: 1562 AN: 3470

East Asian (EAS) AF: 0.823 AC: 4223 AN: 5132

South Asian (SAS) AF: 0.560 AC: 2702 AN: 4824

European-Finnish (FIN) AF: 0.507 AC: 5366 AN: 10594

Middle Eastern (MID) AF: 0.480 AC: 141 AN: 294

European-Non Finnish (NFE) AF: 0.474 AC: 32178 AN: 67926

Other (OTH) AF: 0.452 AC: 953 AN: 2110

Alfa AF: 0.415 Hom.: 1990

Bravo AF: 0.408

Asia WGS AF: 0.617 AC: 2144 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	1.4
DANN	Benign	0.51
PhyloP100		-1.1
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.2
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: rs647451; hg19: chr11-69461731;