2-112165011-G-A

Variant summary

Our verdict is Benign. Variant got -7 ACMG points: 0P and 7B. BP4_Strong BP6_Moderate BP7

The NM_153214.3(FBLN7):c.246G>A(p.Pro82=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00262 in 1,614,006 control chromosomes in the GnomAD database, including 11 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0017 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0027 (11 hom.)
• Consequence: FBLN7 NM_153214.3 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.350

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]

ACMG classification

Verdict is Benign. Variant got -7 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.67).
• BP6: Variant 2-112165011-G-A is Benign according to our data. Variant chr2-112165011-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 2651270.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-0.35 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FBLN7	NM_153214.3	c.246G>A	p.Pro82=	synonymous_variant	3/8	ENST00000331203.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FBLN7	ENST00000331203.7	c.246G>A	p.Pro82=	synonymous_variant	3/8	1	NM_153214.3	P1

Frequencies

GnomAD3 genomes AF: 0.00175 AC: 266 AN: 152156 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000531

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000524

Gnomad ASJ AF: 0.00144

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.00352

Gnomad FIN AF: 0.000283

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00304

Gnomad OTH AF: 0.00144

GnomAD3 exomes AF: 0.00201 AC: 506 AN: 251168 Hom.: 1 AF XY: 0.00208 AC XY: 282 AN XY: 135774

Gnomad AFR exome AF: 0.000615

Gnomad AMR exome AF: 0.000782

Gnomad ASJ exome AF: 0.00228

Gnomad EAS exome AF: 0.000217

Gnomad SAS exome AF: 0.00435

Gnomad FIN exome AF: 0.000277

Gnomad NFE exome AF: 0.00256

Gnomad OTH exome AF: 0.00196

GnomAD4 exome AF: 0.00271 AC: 3964 AN: 1461732 Hom.: 11 Cov.: 30 AF XY: 0.00275 AC XY: 2002 AN XY: 727158

Gnomad4 AFR exome AF: 0.000687

Gnomad4 AMR exome AF: 0.000917

Gnomad4 ASJ exome AF: 0.00253

Gnomad4 EAS exome AF: 0.000101

Gnomad4 SAS exome AF: 0.00481

Gnomad4 FIN exome AF: 0.000468

Gnomad4 NFE exome AF: 0.00291

Gnomad4 OTH exome AF: 0.00230

GnomAD4 genome AF: 0.00175 AC: 266 AN: 152274 Hom.: 0 Cov.: 32 AF XY: 0.00157 AC XY: 117 AN XY: 74452

Gnomad4 AFR AF: 0.000529

Gnomad4 AMR AF: 0.000523

Gnomad4 ASJ AF: 0.00144

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.00352

Gnomad4 FIN AF: 0.000283

Gnomad4 NFE AF: 0.00304

Gnomad4 OTH AF: 0.00142

Alfa AF: 0.00238 Hom.: 0

Bravo AF: 0.00161

Asia WGS AF: 0.00173 AC: 6 AN: 3478

EpiCase AF: 0.00262

EpiControl AF: 0.00184

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Oct 01, 2022

FBLN7: BP4, BP7 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.67
Cadd	Benign	0.55
Dann	Benign	0.82

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.060		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: rs34870326; hg19: chr2-112922588;