Variant 17-443303-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_182705.3(RFLNB):c.296T>C(p.Val99Ala) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00641 in 1,613,968 control chromosomes in the GnomAD database, including 65 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0052 ( 9 hom., cov: 32)

Exomes 𝑓: 0.0065 ( 56 hom. )

Consequence

RFLNB
NM_182705.3 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 8.93

Variant links:

Genes affected

RFLNB (HGNC:28705): (refilin B) Enables filamin binding activity. Predicted to be involved in several processes, including actin filament bundle organization; negative regulation of bone mineralization involved in bone maturation; and negative regulation of chondrocyte development. Predicted to act upstream of or within actin cytoskeleton organization and epithelial to mesenchymal transition. Predicted to be located in actin cytoskeleton. Predicted to be active in actin filament bundle. [provided by Alliance of Genome Resources, Apr 2022]

RFLNB links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0104677975).

BP6

Variant 17-443303-A-G is Benign according to our data. Variant chr17-443303-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 2647162.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAd4 at 9 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RFLNB	NM_182705.3 linkuse as main transcript	c.296T>C	p.Val99Ala	missense_variant	2/2		NP_874364.1	Q8N5W9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RFLNB	ENST00000329099.4 linkuse as main transcript	c.296T>C	p.Val99Ala	missense_variant	2/2	1		ENSP00000331915.4		Q8N5W9

Frequencies

GnomAD3 genomes

AF:

0.00517

AC:

787

AN:

152180

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00123

Gnomad AMI

AF:

0.0406

Gnomad AMR

AF:

0.00144

Gnomad ASJ

AF:

0.00605

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000414

Gnomad FIN

AF:

0.00292

Gnomad MID

AF:

0.00955

Gnomad NFE

AF:

0.00906

Gnomad OTH

AF:

0.00192

GnomAD3 exomes

AF:

0.00488

AC:

1216

AN:

249046

Hom.:

AF XY:

0.00478

AC XY:

646

AN XY:

135200

show subpopulations

Gnomad AFR exome

AF:

0.00110

Gnomad AMR exome

AF:

0.000898

Gnomad ASJ exome

AF:

0.00766

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00154

Gnomad FIN exome

AF:

0.00237

Gnomad NFE exome

AF:

0.00861

Gnomad OTH exome

AF:

0.00364

GnomAD4 exome

AF:

0.00654

AC:

9563

AN:

1461668

Hom.:

Cov.:

AF XY:

0.00651

AC XY:

4732

AN XY:

727126

show subpopulations

Gnomad4 AFR exome

AF:

0.000956

Gnomad4 AMR exome

AF:

0.00112

Gnomad4 ASJ exome

AF:

0.00670

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00139

Gnomad4 FIN exome

AF:

0.00288

Gnomad4 NFE exome

AF:

0.00783

Gnomad4 OTH exome

AF:

0.00514

GnomAD4 genome

AF:

0.00516

AC:

786

AN:

152300

Hom.:

Cov.:

AF XY:

0.00477

AC XY:

355

AN XY:

74472

show subpopulations

Gnomad4 AFR

AF:

0.00123

Gnomad4 AMR

AF:

0.00144

Gnomad4 ASJ

AF:

0.00605

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000414

Gnomad4 FIN

AF:

0.00292

Gnomad4 NFE

AF:

0.00906

Gnomad4 OTH

AF:

0.00190

Alfa

AF:

0.00821

Hom.:

Bravo

AF:

0.00472

TwinsUK

AF:

0.00270

AC:

ALSPAC

AF:

0.00623

AC:

ESP6500AA

AF:

0.000468

AC:

ESP6500EA

AF:

0.00991

AC:

ExAC

AF:

0.00511

AC:

619

Asia WGS

AF:

0.000866

AC:

AN:

3478

EpiCase

AF:

0.00774

EpiControl

AF:

0.00688

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Feb 01, 2023

RFLNB: BP4, BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.21

BayesDel_noAF

Uncertain

-0.070

CADD

Uncertain

DANN

Uncertain

1.0

Eigen

Uncertain

0.50

Eigen_PC

Uncertain

0.58

FATHMM_MKL

Pathogenic

0.99

MetaRNN

Benign

0.010

MetaSVM

Benign

-0.49

PrimateAI

Benign

0.42

PROVEAN

Uncertain

-3.8

REVEL

Benign

0.27

Sift

Uncertain

0.0020

Sift4G

Uncertain

0.0050

MVP

0.28

ClinPred

0.042

GERP RS

5.5

gMVP

0.40

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over