Variant rs9831516 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_015123.3(FRMD4B):c.2840C>T(p.Ser947Leu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.951 in 1,602,998 control chromosomes in the GnomAD database, including 733,282 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.87 ( 59136 hom., cov: 31)

Exomes 𝑓: 0.96 ( 674146 hom. )

Consequence

FRMD4B
NM_015123.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 9.60

Variant links:

Genes affected

FRMD4B (HGNC:24886): (FERM domain containing 4B) This gene encodes a GRP1-binding protein which contains a FERM protein interaction domain as well as two coiled coil domains. This protein may play a role as a scaffolding protein. [provided by RefSeq, Mar 2014]

FRMD4B links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=8.4222E-7).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.985 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FRMD4B	NM_015123.3 linkuse as main transcript	c.2840C>T	p.Ser947Leu	missense_variant	21/23	ENST00000398540.8	NP_055938.2	Q9Y2L6-1B3KNA2Q6PEW6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FRMD4B	ENST00000398540.8 linkuse as main transcript	c.2840C>T	p.Ser947Leu	missense_variant	21/23	1	NM_015123.3	ENSP00000381549.3		Q9Y2L6-1
FRMD4B	ENST00000478263.5 linkuse as main transcript	c.1796C>T	p.Ser599Leu	missense_variant	11/13	1		ENSP00000418682.1		E9PGA7

Frequencies

GnomAD3 genomes

AF:

0.867

AC:

131849

AN:

152000

Hom.:

59129

Cov.:

show subpopulations

Gnomad AFR

AF:

0.644

Gnomad AMI

AF:

1.00

Gnomad AMR

AF:

0.895

Gnomad ASJ

AF:

0.988

Gnomad EAS

AF:

0.606

Gnomad SAS

AF:

0.810

Gnomad FIN

AF:

0.994

Gnomad MID

AF:

0.953

Gnomad NFE

AF:

0.991

Gnomad OTH

AF:

0.896

GnomAD3 exomes

AF:

0.904

AC:

221823

AN:

245344

Hom.:

102349

AF XY:

0.909

AC XY:

120946

AN XY:

133070

show subpopulations

Gnomad AFR exome

AF:

0.642

Gnomad AMR exome

AF:

0.888

Gnomad ASJ exome

AF:

0.991

Gnomad EAS exome

AF:

0.594

Gnomad SAS exome

AF:

0.821

Gnomad FIN exome

AF:

0.992

Gnomad NFE exome

AF:

0.992

Gnomad OTH exome

AF:

0.949

GnomAD4 exome

AF:

0.960

AC:

1392429

AN:

1450880

Hom.:

674146

Cov.:

AF XY:

0.957

AC XY:

689619

AN XY:

720490

show subpopulations

Gnomad4 AFR exome

AF:

0.637

Gnomad4 AMR exome

AF:

0.889

Gnomad4 ASJ exome

AF:

0.991

Gnomad4 EAS exome

AF:

0.619

Gnomad4 SAS exome

AF:

0.822

Gnomad4 FIN exome

AF:

0.992

Gnomad4 NFE exome

AF:

0.994

Gnomad4 OTH exome

AF:

0.937

GnomAD4 genome

AF:

0.867

AC:

131904

AN:

152118

Hom.:

59136

Cov.:

AF XY:

0.863

AC XY:

64181

AN XY:

74368

show subpopulations

Gnomad4 AFR

AF:

0.644

Gnomad4 AMR

AF:

0.895

Gnomad4 ASJ

AF:

0.988

Gnomad4 EAS

AF:

0.606

Gnomad4 SAS

AF:

0.810

Gnomad4 FIN

AF:

0.994

Gnomad4 NFE

AF:

0.991

Gnomad4 OTH

AF:

0.897

Alfa

AF:

0.957

Hom.:

100217

Bravo

AF:

0.850

TwinsUK

AF:

0.995

AC:

3690

ALSPAC

AF:

0.992

AC:

3822

ESP6500AA

AF:

0.652

AC:

2580

ESP6500EA

AF:

0.993

AC:

8250

ExAC

AF:

0.901

AC:

108921

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.14

BayesDel_addAF

Benign

-0.28

BayesDel_noAF

Uncertain

-0.030

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Benign

0.039

T;T

Eigen

Pathogenic

0.84

Eigen_PC

Pathogenic

0.85

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Benign

0.83

T;T

MetaRNN

Benign

8.4e-7

T;T

MetaSVM

Benign

-0.91

MutationAssessor

Uncertain

2.4

M;.

PrimateAI

Uncertain

0.67

PROVEAN

Benign

-1.5

N;N

REVEL

Uncertain

0.46

Sift

Benign

0.10

T;T

Sift4G

Uncertain

0.021

D;D

Polyphen

1.0

D;.

Vest4

0.48

MPC

0.32

ClinPred

0.020

GERP RS

5.8

Varity_R

0.22

gMVP

0.56

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.090

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