1-85581241-G-A

Position:

• chr1-85581241-G-A

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001554.5(CCN1):​c.64-124G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.427 in 1,209,826 control chromosomes in the GnomAD database, including 112,650 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.43 (14219 hom., cov: 31)
  • Exomes 𝑓: 0.43 (98431 hom.)
• Consequence: CCN1 NM_001554.5 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.689

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]

CCN1 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.78).
• BP6: Variant 1-85581241-G-A is Benign according to our data. Variant chr1-85581241-G-A is described in ClinVar as [Benign]. Clinvar id is 1282912.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.558 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CCN1	NM_001554.5	c.64-124G>A		intron_variant		ENST00000451137.7	NP_001545.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CCN1	ENST00000451137.7	c.64-124G>A		intron_variant		1	NM_001554.5	ENSP00000398736.2

Frequencies

GnomAD3 genomes AF: 0.429 AC: 65126 AN: 151722 Hom.: 14199 Cov.: 31

Gnomad AFR AF: 0.443

Gnomad AMI AF: 0.406

Gnomad AMR AF: 0.444

Gnomad ASJ AF: 0.485

Gnomad EAS AF: 0.436

Gnomad SAS AF: 0.576

Gnomad FIN AF: 0.322

Gnomad MID AF: 0.573

Gnomad NFE AF: 0.419

Gnomad OTH AF: 0.449

GnomAD4 exome AF: 0.427 AC: 451412 AN: 1057986 Hom.: 98431 Cov.: 15 AF XY: 0.432 AC XY: 225241 AN XY: 521814

Gnomad4 AFR exome AF: 0.441

Gnomad4 AMR exome AF: 0.441

Gnomad4 ASJ exome AF: 0.474

Gnomad4 EAS exome AF: 0.404

Gnomad4 SAS exome AF: 0.567

Gnomad4 FIN exome AF: 0.336

Gnomad4 NFE exome AF: 0.417

Gnomad4 OTH exome AF: 0.442

GnomAD4 genome AF: 0.429 AC: 65200 AN: 151840 Hom.: 14219 Cov.: 31 AF XY: 0.427 AC XY: 31706 AN XY: 74200

Gnomad4 AFR AF: 0.444

Gnomad4 AMR AF: 0.444

Gnomad4 ASJ AF: 0.485

Gnomad4 EAS AF: 0.437

Gnomad4 SAS AF: 0.576

Gnomad4 FIN AF: 0.322

Gnomad4 NFE AF: 0.419

Gnomad4 OTH AF: 0.447

Alfa AF: 0.429 Hom.: 15313

Bravo AF: 0.436

Asia WGS AF: 0.473 AC: 1642 AN: 3476

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	clinical testing	GeneDx	Nov 11, 2018	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	0.86
DANN	Benign	0.88

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs2297141; hg19: chr1-86046924; COSMIC: COSV71704430; COSMIC: COSV71704430;