rs1057732

Variant names:

• chr8-119424178-T-C
• rs1057732
• NM_002514.4:c.*1046T>C

Variant summary

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

The NM_002514.4(CCN3):​c.*1046T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.183 in 152,162 control chromosomes in the GnomAD database, including 2,752 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 0.18 (2752 hom., cov: 32)
  • Failed GnomAD Quality Control
• Consequence: CCN3 NM_002514.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.511
• Publications: 11 publications found

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]

ENSG00000253398 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.78).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.213 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CCN3	NM_002514.4	c.*1046T>C		3_prime_UTR_variant	Exon 5 of 5	ENST00000259526.4	NP_002505.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CCN3	ENST00000259526.4	c.*1046T>C		3_prime_UTR_variant	Exon 5 of 5	1	NM_002514.4	ENSP00000259526.3
ENSG00000253398	ENST00000519786.1	n.191-4134A>G		intron_variant	Intron 3 of 3	3

Frequencies

GnomAD3 genomes AF: 0.184 AC: 27901 AN: 152046 Hom.: 2749 Cov.: 32

Gnomad AFR AF: 0.166

Gnomad AMI AF: 0.304

Gnomad AMR AF: 0.154

Gnomad ASJ AF: 0.238

Gnomad EAS AF: 0.00346

Gnomad SAS AF: 0.141

Gnomad FIN AF: 0.160

Gnomad MID AF: 0.203

Gnomad NFE AF: 0.216

Gnomad OTH AF: 0.213

GnomAD4 exome Data not reliable, filtered out with message: AC0 AC: 0 AN: 0 Hom.: 0 Cov.: 0 AC XY: 0 AN XY: 0

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AC: 0 AN: 0

Other (OTH) AC: 0 AN: 0

GnomAD4 genome AF: 0.183 AC: 27901 AN: 152162 Hom.: 2752 Cov.: 32 AF XY: 0.180 AC XY: 13390 AN XY: 74386

African (AFR) AF: 0.166 AC: 6897 AN: 41516

American (AMR) AF: 0.154 AC: 2351 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.238 AC: 825 AN: 3468

East Asian (EAS) AF: 0.00347 AC: 18 AN: 5184

South Asian (SAS) AF: 0.142 AC: 685 AN: 4830

European-Finnish (FIN) AF: 0.160 AC: 1697 AN: 10582

Middle Eastern (MID) AF: 0.197 AC: 58 AN: 294

European-Non Finnish (NFE) AF: 0.215 AC: 14647 AN: 67984

Other (OTH) AF: 0.211 AC: 446 AN: 2112

Alfa AF: 0.204 Hom.: 1027

Bravo AF: 0.184

Asia WGS AF: 0.0640 AC: 224 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	4.1
DANN	Benign	0.71
PhyloP100		-0.51
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: rs1057732; hg19: chr8-120436418;