Variant 2-112182792-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_ModerateBP6_ModerateBP7BS2

The NM_153214.3(FBLN7):c.672C>T(p.Asp224=) variant causes a splice region, synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0015 in 1,598,296 control chromosomes in the GnomAD database, including 4 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0011 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0015 ( 4 hom. )

Consequence

FBLN7
NM_153214.3 splice_region, synonymous

Scores

Splicing: ADA: 0.00002447

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.834

Variant links:

Genes affected

FBLN7 (HGNC:26740): (fibulin 7) Predicted to enable calcium ion binding activity; heparan sulfate proteoglycan binding activity; and heparin binding activity. Predicted to be involved in cell adhesion. Predicted to act upstream of or within positive regulation of biomineralization. Located in focal adhesion. [provided by Alliance of Genome Resources, Apr 2022]

FBLN7 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -9 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.46).

BP6

Variant 2-112182792-C-T is Benign according to our data. Variant chr2-112182792-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 2651271.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=0.834 with no splicing effect.

BS2

High Homozygotes in GnomAdExome4 at 4 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FBLN7	NM_153214.3 linkuse as main transcript	c.672C>T	p.Asp224=	splice_region_variant, synonymous_variant	6/8	ENST00000331203.7	NP_694946.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FBLN7	ENST00000331203.7 linkuse as main transcript	c.672C>T	p.Asp224=	splice_region_variant, synonymous_variant	6/8	1	NM_153214.3	ENSP00000331411	P1	Q53RD9-1

Frequencies

GnomAD3 genomes

AF:

0.00111

AC:

169

AN:

152274

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000121

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000131

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.000470

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00228

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.00151

AC:

359

AN:

236996

Hom.:

AF XY:

0.00149

AC XY:

192

AN XY:

128572

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000261

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000430

Gnomad FIN exome

AF:

0.00102

Gnomad NFE exome

AF:

0.00284

Gnomad OTH exome

AF:

0.00124

GnomAD4 exome

AF:

0.00154

AC:

2228

AN:

1445904

Hom.:

Cov.:

AF XY:

0.00161

AC XY:

1159

AN XY:

718768

show subpopulations

Gnomad4 AFR exome

AF:

0.0000917

Gnomad4 AMR exome

AF:

0.000336

Gnomad4 ASJ exome

AF:

0.000116

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000336

Gnomad4 FIN exome

AF:

0.00125

Gnomad4 NFE exome

AF:

0.00184

Gnomad4 OTH exome

AF:

0.00132

GnomAD4 genome

AF:

0.00111

AC:

169

AN:

152392

Hom.:

Cov.:

AF XY:

0.00105

AC XY:

AN XY:

74520

show subpopulations

Gnomad4 AFR

AF:

0.000120

Gnomad4 AMR

AF:

0.000131

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.000470

Gnomad4 NFE

AF:

0.00228

Gnomad4 OTH

AF:

0.000473

Alfa

AF:

0.00224

Hom.:

Bravo

AF:

0.00121

Asia WGS

AF:

0.000866

AC:

AN:

3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Feb 01, 2023

FBLN7: BP4, BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.46

CADD

Benign

DANN

Benign

0.72

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000024

dbscSNV1_RF

Benign

0.0040

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