rs3212891

Variant names:

• chr11-69650739-C-A
• rs3212891
• NM_053056.3:c.724-379C>A

Your query was ambiguous. Multiple possible variants found:

• chr11-69650739-C-A
• chr11-69650739-C-G
• chr11-69650739-C-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.724-379C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.55 in 152,006 control chromosomes in the GnomAD database, including 23,269 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 0.55 (23269 hom., cov: 33)
• Consequence: CCND1 NM_053056.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.120
• Publications: 15 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 = 0.853 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CCND1	NM_053056.3	c.724-379C>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.724-379C>A		intron_variant	Intron 4 of 4	1	NM_053056.3	ENSP00000227507.2
CCND1	ENST00000542367.1	n.187-379C>A		intron_variant	Intron 1 of 1	1

Frequencies

GnomAD3 genomes AF: 0.550 AC: 83520 AN: 151888 Hom.: 23265 Cov.: 33

Gnomad AFR AF: 0.508

Gnomad AMI AF: 0.607

Gnomad AMR AF: 0.495

Gnomad ASJ AF: 0.510

Gnomad EAS AF: 0.874

Gnomad SAS AF: 0.571

Gnomad FIN AF: 0.585

Gnomad MID AF: 0.490

Gnomad NFE AF: 0.557

Gnomad OTH AF: 0.561

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

GnomAD4 genome AF: 0.550 AC: 83549 AN: 152006 Hom.: 23269 Cov.: 33 AF XY: 0.552 AC XY: 41026 AN XY: 74318

African (AFR) AF: 0.508 AC: 21050 AN: 41460

American (AMR) AF: 0.495 AC: 7559 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.510 AC: 1767 AN: 3468

East Asian (EAS) AF: 0.874 AC: 4509 AN: 5158

South Asian (SAS) AF: 0.572 AC: 2755 AN: 4818

European-Finnish (FIN) AF: 0.585 AC: 6199 AN: 10592

Middle Eastern (MID) AF: 0.490 AC: 143 AN: 292

European-Non Finnish (NFE) AF: 0.557 AC: 37832 AN: 67916

Other (OTH) AF: 0.561 AC: 1184 AN: 2112

Alfa AF: 0.555 Hom.: 10796

Bravo AF: 0.542

Asia WGS AF: 0.661 AC: 2296 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	2.3
DANN	Benign	0.79
PhyloP100		-0.12
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: rs3212891; hg19: chr11-69465507;