rs1181702271

Variant names:

• chr3-58008420-G-T
• rs1181702271
• ENST00000490882.5:c.-145G>T

Your query was ambiguous. Multiple possible variants found:

• chr3-58008420-G-T
• chr3-58008420-G-A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The ENST00000490882.5(FLNB):​c.-145G>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000127 in 787,678 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000013 (0 hom.)
• Consequence: FLNB ENST00000490882.5 5_prime_UTR
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.512
• Publications: 0 publications found

Genes affected

FLNB (HGNC:3755): (filamin B) This gene encodes a member of the filamin family. The encoded protein interacts with glycoprotein Ib alpha as part of the process to repair vascular injuries. The platelet glycoprotein Ib complex includes glycoprotein Ib alpha, and it binds the actin cytoskeleton. Mutations in this gene have been found in several conditions: atelosteogenesis type 1 and type 3; boomerang dysplasia; autosomal dominant Larsen syndrome; and spondylocarpotarsal synostosis syndrome. Multiple alternatively spliced transcript variants that encode different protein isoforms have been described for this gene. [provided by RefSeq, Nov 2009]

FLNB Gene-Disease associations (from GenCC):

• atelosteogenesis type I

  Inheritance: AD Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), Orphanet, G2P
• atelosteogenesis type III

  Inheritance: AD Classification: DEFINITIVE, SUPPORTIVE Submitted by: Orphanet, G2P
• Larsen syndrome

  Inheritance: AD Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), Orphanet, G2P
• spondylocarpotarsal synostosis syndrome

  Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), Orphanet, G2P
• Boomerang dysplasia

  Inheritance: AD Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000490882.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FLNB	NM_001457.4	MANE Select	c.-145G>T		upstream_gene	N/A	NP_001448.2	O75369-1
	FLNB	NM_001164317.2		c.-145G>T		upstream_gene	N/A	NP_001157789.1	O75369-8
	FLNB	NM_001164318.2		c.-145G>T		upstream_gene	N/A	NP_001157790.1	O75369-9

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FLNB	ENST00000490882.5	TSL:1	c.-145G>T		5_prime_UTR	Exon 1 of 47	ENSP00000420213.1	O75369-8
	FLNB	ENST00000429972.6	TSL:1	c.-145G>T		5_prime_UTR	Exon 1 of 46	ENSP00000415599.2	O75369-9
	FLNB	ENST00000358537.7	TSL:1	c.-145G>T		5_prime_UTR	Exon 1 of 45	ENSP00000351339.3	O75369-2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000127 AC: 1 AN: 787678 Hom.: 0 Cov.: 11 AF XY: 0.00 AC XY: 0 AN XY: 399358

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 17794

American (AMR) AF: 0.00 AC: 0 AN: 25050

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 16476

East Asian (EAS) AF: 0.00 AC: 0 AN: 28680

South Asian (SAS) AF: 0.00 AC: 0 AN: 53278

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 32828

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2688

European-Non Finnish (NFE) AF: 0.00000174 AC: 1 AN: 574062

Other (OTH) AF: 0.00 AC: 0 AN: 36822

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 0

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	FLNB-Related Spectrum Disorders (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	2.2
DANN	Benign	0.86
PhyloP100		-0.51
PromoterAI		-0.052	Neutral

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

Other links and lift over

dbSNP: rs1181702271; hg19: chr3-57994147;