chr6-41937436-T-A

Variant names:

• chr6-41937436-T-A
• rs2479717
• NM_001760.5:c.415-42A>T

Variant summary

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

The NM_001760.5(CCND3):​c.415-42A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.759 in 1,610,590 control chromosomes in the GnomAD database, including 467,463 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 0.81 (50320 hom., cov: 31)
  • Exomes 𝑓: 0.75 (417143 hom.)
• Consequence: CCND3 NM_001760.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.303
• Publications: 15 publications found

Genes affected

CCND3 (HGNC:1585): (cyclin D3) The protein encoded by this gene belongs to the highly conserved cyclin family, whose members are characterized by a dramatic periodicity in protein abundance through 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 activtiy is required for cell cycle G1/S transition. This protein has been shown to interact with and be involved in the phosphorylation of tumor suppressor protein Rb. The CDK4 activity associated with this cyclin was reported to be necessary for cell cycle progression through G2 phase into mitosis after UV radiation. Several transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Oct 2008]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.942 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CCND3	NM_001760.5	c.415-42A>T		intron_variant	Intron 2 of 4	ENST00000372991.9	NP_001751.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CCND3	ENST00000372991.9	c.415-42A>T		intron_variant	Intron 2 of 4	1	NM_001760.5	ENSP00000362082.5

Frequencies

GnomAD3 genomes AF: 0.807 AC: 122672 AN: 151932 Hom.: 50260 Cov.: 31

Gnomad AFR AF: 0.950

Gnomad AMI AF: 0.726

Gnomad AMR AF: 0.819

Gnomad ASJ AF: 0.644

Gnomad EAS AF: 0.911

Gnomad SAS AF: 0.833

Gnomad FIN AF: 0.750

Gnomad MID AF: 0.653

Gnomad NFE AF: 0.729

Gnomad OTH AF: 0.775

GnomAD2 exomes AF: 0.786 AC: 195697 AN: 249056 AF XY: 0.779

Gnomad AFR exome AF: 0.953

Gnomad AMR exome AF: 0.863

Gnomad ASJ exome AF: 0.655

Gnomad EAS exome AF: 0.910

Gnomad FIN exome AF: 0.755

Gnomad NFE exome AF: 0.727

Gnomad OTH exome AF: 0.755

GnomAD4 exome AF: 0.754 AC: 1099941 AN: 1458540 Hom.: 417143 Cov.: 35 AF XY: 0.755 AC XY: 547346 AN XY: 725150

African (AFR) AF: 0.956 AC: 31953 AN: 33416

American (AMR) AF: 0.859 AC: 38346 AN: 44652

Ashkenazi Jewish (ASJ) AF: 0.656 AC: 17095 AN: 26048

East Asian (EAS) AF: 0.912 AC: 36141 AN: 39638

South Asian (SAS) AF: 0.821 AC: 70798 AN: 86192

European-Finnish (FIN) AF: 0.758 AC: 40283 AN: 53132

Middle Eastern (MID) AF: 0.672 AC: 3775 AN: 5618

European-Non Finnish (NFE) AF: 0.735 AC: 815877 AN: 1109594

Other (OTH) AF: 0.758 AC: 45673 AN: 60250

GnomAD4 genome AF: 0.808 AC: 122794 AN: 152050 Hom.: 50320 Cov.: 31 AF XY: 0.812 AC XY: 60321 AN XY: 74324

African (AFR) AF: 0.950 AC: 39421 AN: 41512

American (AMR) AF: 0.819 AC: 12501 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.644 AC: 2235 AN: 3468

East Asian (EAS) AF: 0.911 AC: 4713 AN: 5176

South Asian (SAS) AF: 0.833 AC: 4004 AN: 4808

European-Finnish (FIN) AF: 0.750 AC: 7925 AN: 10568

Middle Eastern (MID) AF: 0.661 AC: 193 AN: 292

European-Non Finnish (NFE) AF: 0.729 AC: 49503 AN: 67940

Other (OTH) AF: 0.774 AC: 1637 AN: 2114

Alfa AF: 0.758 Hom.: 8096

Bravo AF: 0.819

Asia WGS AF: 0.864 AC: 3005 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	4.2
DANN	Benign	0.71
PhyloP100		0.30
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
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: rs2479717; hg19: chr6-41905174;