rs12634123

Variant names:

• chr3-58159536-G-A
• rs12634123
• NM_001457.4:c.6889-18G>A

Your query was ambiguous. Multiple possible variants found:

• chr3-58159536-G-A
• chr3-58159536-G-C
• chr3-58159536-G-T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001457.4(FLNB):​c.6889-18G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.64 in 1,612,544 control chromosomes in the GnomAD database, including 335,250 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.64 (31631 hom., cov: 32)
  • Exomes 𝑓: 0.64 (303619 hom.)
• Consequence: FLNB NM_001457.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:6
• Conservation: PhyloP100: 0.113
• Publications: 13 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), G2P, Orphanet
• atelosteogenesis type III

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

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

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

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

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.55).
• BP6: Variant 3-58159536-G-A is Benign according to our data. Variant chr3-58159536-G-A is described in ClinVar as Benign. ClinVar VariationId is 258119.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.974 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FLNB	NM_001457.4	c.6889-18G>A		intron_variant	Intron 41 of 45	ENST00000295956.9	NP_001448.2
FLNB	NM_001164317.2	c.6982-18G>A		intron_variant	Intron 42 of 46		NP_001157789.1
FLNB	NM_001164318.2	c.6856-18G>A		intron_variant	Intron 41 of 45		NP_001157790.1
FLNB	NM_001164319.2	c.6817-18G>A		intron_variant	Intron 40 of 44		NP_001157791.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FLNB	ENST00000295956.9	c.6889-18G>A		intron_variant	Intron 41 of 45	1	NM_001457.4	ENSP00000295956.5

Frequencies

GnomAD3 genomes AF: 0.640 AC: 97172 AN: 151944 Hom.: 31602 Cov.: 32

Gnomad AFR AF: 0.625

Gnomad AMI AF: 0.633

Gnomad AMR AF: 0.687

Gnomad ASJ AF: 0.622

Gnomad EAS AF: 0.997

Gnomad SAS AF: 0.772

Gnomad FIN AF: 0.545

Gnomad MID AF: 0.589

Gnomad NFE AF: 0.617

Gnomad OTH AF: 0.641

GnomAD2 exomes AF: 0.672 AC: 168874 AN: 251232 AF XY: 0.669

Gnomad AFR exome AF: 0.625

Gnomad AMR exome AF: 0.746

Gnomad ASJ exome AF: 0.627

Gnomad EAS exome AF: 0.999

Gnomad FIN exome AF: 0.548

Gnomad NFE exome AF: 0.612

Gnomad OTH exome AF: 0.658

GnomAD4 exome AF: 0.640 AC: 935294 AN: 1460482 Hom.: 303619 Cov.: 39 AF XY: 0.642 AC XY: 466791 AN XY: 726608

African (AFR) AF: 0.615 AC: 20587 AN: 33450

American (AMR) AF: 0.741 AC: 33117 AN: 44718

Ashkenazi Jewish (ASJ) AF: 0.623 AC: 16275 AN: 26128

East Asian (EAS) AF: 0.999 AC: 39658 AN: 39700

South Asian (SAS) AF: 0.738 AC: 63638 AN: 86230

European-Finnish (FIN) AF: 0.551 AC: 29390 AN: 53306

Middle Eastern (MID) AF: 0.644 AC: 3712 AN: 5766

European-Non Finnish (NFE) AF: 0.620 AC: 688853 AN: 1110830

Other (OTH) AF: 0.664 AC: 40064 AN: 60354

GnomAD4 genome AF: 0.640 AC: 97251 AN: 152062 Hom.: 31631 Cov.: 32 AF XY: 0.644 AC XY: 47819 AN XY: 74308

African (AFR) AF: 0.625 AC: 25915 AN: 41476

American (AMR) AF: 0.687 AC: 10505 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.622 AC: 2159 AN: 3470

East Asian (EAS) AF: 0.997 AC: 5162 AN: 5180

South Asian (SAS) AF: 0.771 AC: 3720 AN: 4822

European-Finnish (FIN) AF: 0.545 AC: 5751 AN: 10546

Middle Eastern (MID) AF: 0.605 AC: 178 AN: 294

European-Non Finnish (NFE) AF: 0.617 AC: 41921 AN: 67960

Other (OTH) AF: 0.646 AC: 1363 AN: 2110

Alfa AF: 0.636 Hom.: 8032

Bravo AF: 0.650

Asia WGS AF: 0.878 AC: 3054 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:4

-

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

-

Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Feb 01, 2016

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

-

Genome Diagnostics Laboratory, Amsterdam University Medical Center

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

not provided Benign:2

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.55
CADD	Benign	9.9
DANN	Benign	0.85
PhyloP100		0.11
Mutation Taster		=100/0	polymorphism (auto)

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: rs12634123; hg19: chr3-58145263;