2-112182792-C-T

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BP4_Moderate BP6_Moderate BP7

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

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 Likely_benign. Variant got -5 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.

Transcripts

RefSeq

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

Ensembl

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

Frequencies

GnomAD3 genomes AF: 0.00111 AC: 169 AN: 152274 Hom.: 0 Cov.: 33

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.: 0 AF XY: 0.00149 AC XY: 192 AN XY: 128572

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.: 4 Cov.: 31 AF XY: 0.00161 AC XY: 1159 AN XY: 718768

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.: 0 Cov.: 33 AF XY: 0.00105 AC XY: 78 AN XY: 74520

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.: 1

Bravo AF: 0.00121

Asia WGS AF: 0.000866 AC: 3 AN: 3478

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

Feb 01, 2023

FBLN7: BP4, BS2 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.46
Cadd	Benign	14
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

Other links and lift over

dbSNP: rs147423265; hg19: chr2-112940369; COSMIC: COSV55616600; COSMIC: COSV55616600;