Variant chr6-112054634-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_198239.2(CCN6):c.48+229G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.008 in 541,248 control chromosomes in the GnomAD database, including 27 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0072 ( 6 hom., cov: 32)

Exomes 𝑓: 0.0083 ( 21 hom. )

Consequence

CCN6
NM_198239.2 intron

Scores

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -1.77

Variant links:

Genes affected

CCN6 (HGNC:12771): (cellular communication network factor 6) This gene encodes a member of the WNT1 inducible signaling pathway (WISP) protein subfamily, which belongs to the connective tissue growth factor (CTGF) family. WNT1 is a member of a family of cysteine-rich, glycosylated signaling proteins that mediate diverse developmental processes. The CTGF family members are characterized by four conserved cysteine-rich domains: insulin-like growth factor-binding domain, von Willebrand factor type C module, thrombospondin domain and C-terminal cystine knot-like domain. This gene is overexpressed in colon tumors. It may be downstream in the WNT1 signaling pathway that is relevant to malignant transformation. Mutations of this gene are associated with progressive pseudorheumatoid dysplasia, an autosomal recessive skeletal disorder, indicating that the gene is essential for normal postnatal skeletal growth and cartilage homeostasis. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]

CCN6 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.89).

BP6

Variant 6-112054634-G-A is Benign according to our data. Variant chr6-112054634-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 1335640.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.00719 (1095/152190) while in subpopulation NFE AF= 0.00985 (670/68004). AF 95% confidence interval is 0.00923. There are 6 homozygotes in gnomad4. There are 517 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 6 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CCN6	NM_198239.2 linkuse as main transcript	c.48+229G>A		intron_variant		ENST00000368666.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CCN6	ENST00000368666.7 linkuse as main transcript	c.48+229G>A		intron_variant		1	NM_198239.2	P1	O95389-1

Frequencies

GnomAD3 genomes

AF:

0.00719

AC:

1094

AN:

152072

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00172

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00798

Gnomad ASJ

AF:

0.00952

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000829

Gnomad FIN

AF:

0.0164

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.00985

Gnomad OTH

AF:

0.00908

GnomAD4 exome

AF:

0.00832

AC:

3237

AN:

389058

Hom.:

Cov.:

AF XY:

0.00816

AC XY:

1705

AN XY:

208890

show subpopulations

Gnomad4 AFR exome

AF:

0.00127

Gnomad4 AMR exome

AF:

0.00608

Gnomad4 ASJ exome

AF:

0.00995

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000659

Gnomad4 FIN exome

AF:

0.0205

Gnomad4 NFE exome

AF:

0.00998

Gnomad4 OTH exome

AF:

0.00864

GnomAD4 genome

AF:

0.00719

AC:

1095

AN:

152190

Hom.:

Cov.:

AF XY:

0.00695

AC XY:

517

AN XY:

74382

show subpopulations

Gnomad4 AFR

AF:

0.00171

Gnomad4 AMR

AF:

0.00797

Gnomad4 ASJ

AF:

0.00952

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00104

Gnomad4 FIN

AF:

0.0164

Gnomad4 NFE

AF:

0.00985

Gnomad4 OTH

AF:

0.00899

Alfa

AF:

0.0100

Hom.:

Bravo

AF:

0.00659

Asia WGS

AF:

0.000577

AC:

AN:

3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Likely benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Mar 01, 2024	CCN6: BP4, BP7, BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.89

CADD

Benign

0.53

DANN

Benign

0.69

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over