rs9658584

Positions:

• chr1-85581628-G-C

Variant summary

Our verdict is Benign. Variant got -18 ACMG points: 0P and 18B. BP4_Moderate BP6_Very_Strong BA1

The NM_001554.5(CCN1):​c.277+50G>C variant causes a intron change. The variant allele was found at a frequency of 0.193 in 1,573,466 control chromosomes in the GnomAD database, including 30,707 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.16 (2266 hom., cov: 33)
  • Exomes 𝑓: 0.20 (28441 hom.)
• Consequence: CCN1 NM_001554.5 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 4.08

Genes affected

CCN1 (HGNC:2654): (cellular communication network factor 1) The secreted protein encoded by this gene is growth factor-inducible and promotes the adhesion of endothelial cells. The encoded protein interacts with several integrins and with heparan sulfate proteoglycan. This protein also plays a role in cell proliferation, differentiation, angiogenesis, apoptosis, and extracellular matrix formation. [provided by RefSeq, Sep 2011]

ACMG classification

Verdict is Benign. Variant got -18 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.35).
• BP6: Variant 1-85581628-G-C is Benign according to our data. Variant chr1-85581628-G-C is described in ClinVar as [Benign]. Clinvar id is 1178850.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.202 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CCN1	NM_001554.5	c.277+50G>C		intron_variant		ENST00000451137.7	NP_001545.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CCN1	ENST00000451137.7	c.277+50G>C		intron_variant		1	NM_001554.5	ENSP00000398736	P1

Frequencies

GnomAD3 genomes AF: 0.156 AC: 23771 AN: 152102 Hom.: 2269 Cov.: 33

Gnomad AFR AF: 0.0510

Gnomad AMI AF: 0.293

Gnomad AMR AF: 0.207

Gnomad ASJ AF: 0.182

Gnomad EAS AF: 0.139

Gnomad SAS AF: 0.154

Gnomad FIN AF: 0.163

Gnomad MID AF: 0.187

Gnomad NFE AF: 0.205

Gnomad OTH AF: 0.187

GnomAD3 exomes AF: 0.189 AC: 41387 AN: 219016 Hom.: 4055 AF XY: 0.188 AC XY: 22407 AN XY: 119032

Gnomad AFR exome AF: 0.0484

Gnomad AMR exome AF: 0.258

Gnomad ASJ exome AF: 0.189

Gnomad EAS exome AF: 0.137

Gnomad SAS exome AF: 0.161

Gnomad FIN exome AF: 0.158

Gnomad NFE exome AF: 0.210

Gnomad OTH exome AF: 0.204

GnomAD4 exome AF: 0.197 AC: 279502 AN: 1421246 Hom.: 28441 Cov.: 26 AF XY: 0.196 AC XY: 137958 AN XY: 704206

Gnomad4 AFR exome AF: 0.0448

Gnomad4 AMR exome AF: 0.248

Gnomad4 ASJ exome AF: 0.181

Gnomad4 EAS exome AF: 0.143

Gnomad4 SAS exome AF: 0.160

Gnomad4 FIN exome AF: 0.161

Gnomad4 NFE exome AF: 0.206

Gnomad4 OTH exome AF: 0.188

GnomAD4 genome AF: 0.156 AC: 23762 AN: 152220 Hom.: 2266 Cov.: 33 AF XY: 0.155 AC XY: 11523 AN XY: 74422

Gnomad4 AFR AF: 0.0509

Gnomad4 AMR AF: 0.207

Gnomad4 ASJ AF: 0.182

Gnomad4 EAS AF: 0.138

Gnomad4 SAS AF: 0.154

Gnomad4 FIN AF: 0.163

Gnomad4 NFE AF: 0.205

Gnomad4 OTH AF: 0.188

Alfa AF: 0.179 Hom.: 505

Bravo AF: 0.161

Asia WGS AF: 0.112 AC: 390 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Nov 12, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.35
CADD	Benign	21
DANN	Benign	0.91

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: rs9658584; hg19: chr1-86047311;