NM_001554.5:c.277+50G>C

Variant names:

• chr1-85581628-G-C
• rs9658584
• NM_001554.5:c.277+50G>C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 10 publications found

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

Our verdict: Benign. The variant received -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 VariationId 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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001554.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CCN1	NM_001554.5	MANE Select	c.277+50G>C		intron	N/A	NP_001545.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CCN1	ENST00000451137.7	TSL:1 MANE Select	c.277+50G>C		intron	N/A	ENSP00000398736.2
	CCN1	ENST00000674743.1		n.390G>C		non_coding_transcript_exon	Exon 2 of 4
	CCN1	ENST00000480413.1	TSL:2	n.379+50G>C		intron	N/A

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

GnomAD2 exomes AF: 0.189 AC: 41387 AN: 219016 AF XY: 0.188

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 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

African (AFR) AF: 0.0448 AC: 1452 AN: 32408

American (AMR) AF: 0.248 AC: 10102 AN: 40802

Ashkenazi Jewish (ASJ) AF: 0.181 AC: 4571 AN: 25294

East Asian (EAS) AF: 0.143 AC: 5579 AN: 38906

South Asian (SAS) AF: 0.160 AC: 13412 AN: 83616

European-Finnish (FIN) AF: 0.161 AC: 8367 AN: 51902

Middle Eastern (MID) AF: 0.226 AC: 1263 AN: 5578

European-Non Finnish (NFE) AF: 0.206 AC: 223750 AN: 1084064

Other (OTH) AF: 0.188 AC: 11006 AN: 58676

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

African (AFR) AF: 0.0509 AC: 2115 AN: 41550

American (AMR) AF: 0.207 AC: 3165 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.182 AC: 631 AN: 3468

East Asian (EAS) AF: 0.138 AC: 717 AN: 5184

South Asian (SAS) AF: 0.154 AC: 742 AN: 4822

European-Finnish (FIN) AF: 0.163 AC: 1727 AN: 10586

Middle Eastern (MID) AF: 0.187 AC: 55 AN: 294

European-Non Finnish (NFE) AF: 0.205 AC: 13947 AN: 67988

Other (OTH) AF: 0.188 AC: 396 AN: 2112

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

Nov 12, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.35
CADD	Benign	21
DANN	Benign	0.91
PhyloP100		4.1
Mutation Taster		=55/45	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: rs9658584; hg19: chr1-86047311;