rs80356518

Variant names:

• chr3-58163161-T-C
• rs80356518
• NM_001457.4:c.7029T>C

Your query was ambiguous. Multiple possible variants found:

• chr3-58163161-T-C
• chr3-58163161-T-G

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 2P and 7B. PM2 BP4_Strong BP6_Moderate BP7

The NM_001457.4(FLNB):​c.7029T>C​(p.Tyr2343Tyr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000197 in 152,228 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 Likely benign (★).

• Frequency: Genomes: 𝑓 0.000020 (0 hom., cov: 32)
• Consequence: FLNB NM_001457.4 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -3.00
• Publications: 2 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-AS1 (HGNC:40239): (FLNB antisense RNA 1)

ACMG classification

Our verdict: Likely_benign. The variant received -5 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).
• BP6: Variant 3-58163161-T-C is Benign according to our data. Variant chr3-58163161-T-C is described in ClinVar as Likely_benign. ClinVar VariationId is 2870093.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-3 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001457.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FLNB	NM_001457.4	MANE Select	c.7029T>C	p.Tyr2343Tyr	synonymous	Exon 43 of 46	NP_001448.2
	FLNB	NM_001164317.2		c.7122T>C	p.Tyr2374Tyr	synonymous	Exon 44 of 47	NP_001157789.1
	FLNB	NM_001164318.2		c.6996T>C	p.Tyr2332Tyr	synonymous	Exon 43 of 46	NP_001157790.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FLNB	ENST00000295956.9	TSL:1 MANE Select	c.7029T>C	p.Tyr2343Tyr	synonymous	Exon 43 of 46	ENSP00000295956.5
	FLNB	ENST00000490882.5	TSL:1	c.7122T>C	p.Tyr2374Tyr	synonymous	Exon 44 of 47	ENSP00000420213.1
	FLNB	ENST00000429972.6	TSL:1	c.6996T>C	p.Tyr2332Tyr	synonymous	Exon 43 of 46	ENSP00000415599.2

Frequencies

GnomAD3 genomes AF: 0.0000197 AC: 3 AN: 152228 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000723

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome Cov.: 30

GnomAD4 genome AF: 0.0000197 AC: 3 AN: 152228 Hom.: 0 Cov.: 32 AF XY: 0.0000269 AC XY: 2 AN XY: 74362

African (AFR) AF: 0.0000723 AC: 3 AN: 41470

American (AMR) AF: 0.00 AC: 0 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5200

South Asian (SAS) AF: 0.00 AC: 0 AN: 4826

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10620

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68032

Other (OTH) AF: 0.00 AC: 0 AN: 2092

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

ClinVar submissions as Germline

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	0.022
DANN	Benign	0.46
PhyloP100		-3.0

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: rs80356518; hg19: chr3-58148888;