rs1352075

Variant names:

• chr11-69642525-C-T
• rs1352075
• NM_053056.3:c.199-506C>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.199-506C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.429 in 152,084 control chromosomes in the GnomAD database, including 15,332 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 0.43 (15332 hom., cov: 33)
• Consequence: CCND1 NM_053056.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.41
• Publications: 19 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=-0.75).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.803 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CCND1	NM_053056.3	c.199-506C>T		intron_variant	Intron 1 of 4	ENST00000227507.3	NP_444284.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CCND1	ENST00000227507.3	c.199-506C>T		intron_variant	Intron 1 of 4	1	NM_053056.3	ENSP00000227507.2
CCND1	ENST00000536559.1	c.198+1014C>T		intron_variant	Intron 1 of 1	3		ENSP00000438482.1
CCND1	ENST00000535993.1	n.282-506C>T		intron_variant	Intron 1 of 1	2
CCND1	ENST00000539241.1	n.348-506C>T		intron_variant	Intron 1 of 2	2

Frequencies

GnomAD3 genomes AF: 0.429 AC: 65187 AN: 151966 Hom.: 15334 Cov.: 33

Gnomad AFR AF: 0.245

Gnomad AMI AF: 0.413

Gnomad AMR AF: 0.419

Gnomad ASJ AF: 0.495

Gnomad EAS AF: 0.824

Gnomad SAS AF: 0.602

Gnomad FIN AF: 0.509

Gnomad MID AF: 0.497

Gnomad NFE AF: 0.484

Gnomad OTH AF: 0.458

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

GnomAD4 genome AF: 0.429 AC: 65199 AN: 152084 Hom.: 15332 Cov.: 33 AF XY: 0.436 AC XY: 32410 AN XY: 74356

African (AFR) AF: 0.245 AC: 10184 AN: 41524

American (AMR) AF: 0.419 AC: 6406 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.495 AC: 1719 AN: 3470

East Asian (EAS) AF: 0.824 AC: 4237 AN: 5142

South Asian (SAS) AF: 0.604 AC: 2913 AN: 4826

European-Finnish (FIN) AF: 0.509 AC: 5388 AN: 10584

Middle Eastern (MID) AF: 0.490 AC: 144 AN: 294

European-Non Finnish (NFE) AF: 0.484 AC: 32864 AN: 67934

Other (OTH) AF: 0.460 AC: 970 AN: 2110

Alfa AF: 0.469 Hom.: 34976

Bravo AF: 0.414

Asia WGS AF: 0.628 AC: 2178 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.75
CADD	Benign	17
DANN	Benign	0.84
PhyloP100		2.4
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs1352075; hg19: chr11-69457293; COSMIC: COSV57123535; COSMIC: COSV57123535;