3-58008468-C-T

Variant names:

• chr3-58008468-C-T
• rs150348065
• NM_001457.4:c.-97C>T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

The NM_001457.4(FLNB):​c.-97C>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 0.000904 in 1,429,856 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0011 (0 hom., cov: 33)
  • Exomes 𝑓: 0.00088 (2 hom.)
• Consequence: FLNB NM_001457.4 5_prime_UTR
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.814
• 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: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.58).
• BP6: Variant 3-58008468-C-T is Benign according to our data. Variant chr3-58008468-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 902963.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population amr. GnomAd4 allele frequency = 0.00111 (169/152272) while in subpopulation AMR AF = 0.00398 (61/15308). AF 95% confidence interval is 0.00318. There are 0 homozygotes in GnomAd4. There are 78 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.
• BS2: High Homozygotes in GnomAdExome4 at 2 AR,AD gene

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FLNB	NM_001457.4	MANE Select	c.-97C>T		5_prime_UTR	Exon 1 of 46	NP_001448.2	O75369-1
	FLNB	NM_001164317.2		c.-97C>T		5_prime_UTR	Exon 1 of 47	NP_001157789.1	O75369-8
	FLNB	NM_001164318.2		c.-97C>T		5_prime_UTR	Exon 1 of 46	NP_001157790.1	O75369-9

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FLNB	ENST00000295956.9	TSL:1 MANE Select	c.-97C>T		5_prime_UTR	Exon 1 of 46	ENSP00000295956.5	O75369-1
	FLNB	ENST00000490882.5	TSL:1	c.-97C>T		5_prime_UTR	Exon 1 of 47	ENSP00000420213.1	O75369-8
	FLNB	ENST00000429972.6	TSL:1	c.-97C>T		5_prime_UTR	Exon 1 of 46	ENSP00000415599.2	O75369-9

Frequencies

GnomAD3 genomes AF: 0.00110 AC: 168 AN: 152156 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.000748

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00399

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000414

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00318

Gnomad NFE AF: 0.000868

Gnomad OTH AF: 0.00670

GnomAD4 exome AF: 0.000880 AC: 1124 AN: 1277584 Hom.: 2 Cov.: 19 AF XY: 0.000885 AC XY: 563 AN XY: 635988

African (AFR) AF: 0.00123 AC: 36 AN: 29166

American (AMR) AF: 0.00276 AC: 98 AN: 35526

Ashkenazi Jewish (ASJ) AF: 0.000123 AC: 3 AN: 24374

East Asian (EAS) AF: 0.00 AC: 0 AN: 35186

South Asian (SAS) AF: 0.000301 AC: 23 AN: 76514

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 46934

Middle Eastern (MID) AF: 0.0144 AC: 55 AN: 3816

European-Non Finnish (NFE) AF: 0.000825 AC: 802 AN: 972166

Other (OTH) AF: 0.00199 AC: 107 AN: 53902

GnomAD4 genome AF: 0.00111 AC: 169 AN: 152272 Hom.: 0 Cov.: 33 AF XY: 0.00105 AC XY: 78 AN XY: 74470

African (AFR) AF: 0.000770 AC: 32 AN: 41580

American (AMR) AF: 0.00398 AC: 61 AN: 15308

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5182

South Asian (SAS) AF: 0.000414 AC: 2 AN: 4832

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10606

Middle Eastern (MID) AF: 0.00342 AC: 1 AN: 292

European-Non Finnish (NFE) AF: 0.000868 AC: 59 AN: 67982

Other (OTH) AF: 0.00664 AC: 14 AN: 2108

Alfa AF: 0.000212 Hom.: 0

Bravo AF: 0.00153

Asia WGS AF: 0.000577 AC: 2 AN: 3478

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	1	FLNB-Related Spectrum Disorders (1)
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.58
CADD	Benign	16
DANN	Benign	0.96
PhyloP100		0.81
PromoterAI		-0.069	Neutral
Mutation Taster		=298/2	polymorphism

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: rs150348065; hg19: chr3-57994195;