rs3918298

Variant names:

• chr11-69648505-G-A
• rs3918298
• NM_053056.3:c.723+363G>A

Variant summary

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

The NM_053056.3(CCND1):​c.723+363G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0916 in 152,284 control chromosomes in the GnomAD database, including 1,352 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 0.092 (1352 hom., cov: 34)
• Consequence: CCND1 NM_053056.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.251
• Publications: 17 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=-0.85).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.243 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CCND1	NM_053056.3	c.723+363G>A		intron_variant	Intron 4 of 4	ENST00000227507.3	NP_444284.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CCND1	ENST00000227507.3	c.723+363G>A		intron_variant	Intron 4 of 4	1	NM_053056.3	ENSP00000227507.2
CCND1	ENST00000542367.1	n.186+363G>A		intron_variant	Intron 1 of 1	1

Frequencies

GnomAD3 genomes AF: 0.0914 AC: 13906 AN: 152166 Hom.: 1344 Cov.: 34

Gnomad AFR AF: 0.247

Gnomad AMI AF: 0.0121

Gnomad AMR AF: 0.0549

Gnomad ASJ AF: 0.0260

Gnomad EAS AF: 0.0158

Gnomad SAS AF: 0.100

Gnomad FIN AF: 0.00339

Gnomad MID AF: 0.0601

Gnomad NFE AF: 0.0283

Gnomad OTH AF: 0.0890

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

GnomAD4 genome AF: 0.0916 AC: 13947 AN: 152284 Hom.: 1352 Cov.: 34 AF XY: 0.0899 AC XY: 6694 AN XY: 74460

African (AFR) AF: 0.247 AC: 10266 AN: 41518

American (AMR) AF: 0.0547 AC: 838 AN: 15310

Ashkenazi Jewish (ASJ) AF: 0.0260 AC: 90 AN: 3468

East Asian (EAS) AF: 0.0158 AC: 82 AN: 5184

South Asian (SAS) AF: 0.100 AC: 483 AN: 4824

European-Finnish (FIN) AF: 0.00339 AC: 36 AN: 10624

Middle Eastern (MID) AF: 0.0612 AC: 18 AN: 294

European-Non Finnish (NFE) AF: 0.0283 AC: 1928 AN: 68038

Other (OTH) AF: 0.0923 AC: 195 AN: 2112

Alfa AF: 0.0724 Hom.: 258

Bravo AF: 0.0998

Asia WGS AF: 0.100 AC: 351 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	10
DANN	Benign	0.81
PhyloP100		0.25
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: rs3918298; hg19: chr11-69463273; COSMIC: COSV57119919;