Variant rs751371914 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 5P and 2B. PM1PM2PP2BP4_Moderate

The NM_001457.4(FLNB):c.199C>A(p.His67Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,680 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. H67Y) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

FLNB
NM_001457.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.95

Variant links:

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 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 3 ACMG points.

PM1

In a region_of_interest Actin-binding (size 238) in uniprot entity FLNB_HUMAN there are 58 pathogenic changes around while only 5 benign (92%) in NM_001457.4

PM2

Very rare variant in population databases, with high coverage;

PP2

Missense variant where missense usually causes diseases, FLNB

BP4

Computational evidence support a benign effect (MetaRNN=0.25884205).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
FLNB	NM_001457.4 linkuse as main transcript	c.199C>A	p.His67Asn	missense_variant	1/46	ENST00000295956.9
FLNB	NM_001164317.2 linkuse as main transcript	c.199C>A	p.His67Asn	missense_variant	1/47
FLNB	NM_001164318.2 linkuse as main transcript	c.199C>A	p.His67Asn	missense_variant	1/46
FLNB	NM_001164319.2 linkuse as main transcript	c.199C>A	p.His67Asn	missense_variant	1/45

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FLNB	ENST00000295956.9 linkuse as main transcript	c.199C>A	p.His67Asn	missense_variant	1/46	1	NM_001457.4	A1	O75369-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000398

AC:

AN:

251338

Hom.:

AF XY:

0.00000736

AC XY:

AN XY:

135862

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000880

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

6.84e-7

AC:

AN:

1461680

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

727114

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

8.99e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Alfa

AF:

0.0000936

Hom.:

ExAC

AF:

0.00000824

AC:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Uncertain

0.040

BayesDel_noAF

Benign

-0.18

CADD

Uncertain

DANN

Benign

0.97

Eigen

Benign

0.020

Eigen_PC

Benign

0.21

FATHMM_MKL

Uncertain

0.92

LIST_S2

Uncertain

0.87

D;D;D;D

M_CAP

Uncertain

0.14

MetaRNN

Benign

0.26

T;T;T;T

MetaSVM

Uncertain

0.29

MutationAssessor

Benign

-0.98

N;N;N;N

MutationTaster

Benign

1.0

D;D;D;D;D;D

PrimateAI

Uncertain

0.70

PROVEAN

Benign

-0.73

N;N;N;N

REVEL

Uncertain

0.48

Sift

Benign

0.61

T;T;T;T

Sift4G

Benign

1.0

T;T;T;T

Polyphen

1.0, 0.68

.;D;P;.

Vest4

0.26

MutPred

0.52

Loss of glycosylation at P70 (P = 0.0359);Loss of glycosylation at P70 (P = 0.0359);Loss of glycosylation at P70 (P = 0.0359);Loss of glycosylation at P70 (P = 0.0359);

MVP

0.94

MPC

1.3

ClinPred

0.50

GERP RS

5.5

Varity_R

0.53

gMVP

0.60

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over