rs2071518

chr8-119423572-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_002514.4(CCN3):c.*440C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.332 in 153,434 control chromosomes in the GnomAD database, including 10,055 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 0.33 (10009 hom., cov: 32)
  • Exomes 𝑓: 0.23 (46 hom.)
• Consequence: CCN3 NM_002514.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.85

Genes affected

CCN3 (HGNC:7885): (cellular communication network factor 3) The protein encoded by this gene is a small secreted cysteine-rich protein and a member of the CCN family of regulatory proteins. CNN family proteins associate with the extracellular matrix and play an important role in cardiovascular and skeletal development, fibrosis and cancer development. [provided by RefSeq, Feb 2009]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.545 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CCN3	NM_002514.4	c.*440C>T		3_prime_UTR_variant	5/5	ENST00000259526.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CCN3	ENST00000259526.4	c.*440C>T		3_prime_UTR_variant	5/5	1	NM_002514.4	P1
	ENST00000519786.1	n.191-3528G>A		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.333 AC: 50526 AN: 151952 Hom.: 9968 Cov.: 32

Gnomad AFR AF: 0.550

Gnomad AMI AF: 0.340

Gnomad AMR AF: 0.232

Gnomad ASJ AF: 0.374

Gnomad EAS AF: 0.150

Gnomad SAS AF: 0.318

Gnomad FIN AF: 0.183

Gnomad MID AF: 0.253

Gnomad NFE AF: 0.259

Gnomad OTH AF: 0.337

GnomAD4 exome AF: 0.235 AC: 320 AN: 1364 Hom.: 46 Cov.: 0 AF XY: 0.233 AC XY: 159 AN XY: 682

Gnomad4 AFR exome AF: 0.591

Gnomad4 AMR exome AF: 0.180

Gnomad4 ASJ exome AF: 0.536

Gnomad4 EAS exome AF: 0.136

Gnomad4 SAS exome AF: 0.231

Gnomad4 FIN exome AF: 0.250

Gnomad4 NFE exome AF: 0.225

Gnomad4 OTH exome AF: 0.350

GnomAD4 genome AF: 0.333 AC: 50606 AN: 152070 Hom.: 10009 Cov.: 32 AF XY: 0.326 AC XY: 24270 AN XY: 74364

Gnomad4 AFR AF: 0.551

Gnomad4 AMR AF: 0.232

Gnomad4 ASJ AF: 0.374

Gnomad4 EAS AF: 0.151

Gnomad4 SAS AF: 0.318

Gnomad4 FIN AF: 0.183

Gnomad4 NFE AF: 0.259

Gnomad4 OTH AF: 0.335

Alfa AF: 0.276 Hom.: 9049

Bravo AF: 0.345

Asia WGS AF: 0.266 AC: 926 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
Cadd	Benign	5.4
Dann	Benign	0.26

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

Publications

LitVar

Other links and lift over

dbSNP: rs2071518; hg19: chr8-120435812;