Variant 3-69181073-C-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_ModerateBP6_ModerateBS2

The NM_015123.3(FRMD4B):c.2677G>T(p.Ala893Ser) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00169 in 1,613,968 control chromosomes in the GnomAD database, including 6 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0015 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0017 ( 6 hom. )

Consequence

FRMD4B
NM_015123.3 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 7.57

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 -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.1034182).

BP6

Variant 3-69181073-C-A is Benign according to our data. Variant chr3-69181073-C-A is described in ClinVar as [Likely_benign]. Clinvar id is 782988.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAdExome at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FRMD4B	NM_015123.3 linkuse as main transcript	c.2677G>T	p.Ala893Ser	missense_variant	21/23	ENST00000398540.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FRMD4B	ENST00000398540.8 linkuse as main transcript	c.2677G>T	p.Ala893Ser	missense_variant	21/23	1	NM_015123.3	P1	Q9Y2L6-1
FRMD4B	ENST00000478263.5 linkuse as main transcript	c.1633G>T	p.Ala545Ser	missense_variant	11/13	1

Frequencies

GnomAD3 genomes

AF:

0.00146

AC:

222

AN:

152144

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000217

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000458

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00321

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00245

Gnomad OTH

AF:

0.00239

GnomAD3 exomes

AF:

0.00144

AC:

360

AN:

249226

Hom.:

AF XY:

0.00144

AC XY:

195

AN XY:

135210

show subpopulations

Gnomad AFR exome

AF:

0.000258

Gnomad AMR exome

AF:

0.000145

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00330

Gnomad NFE exome

AF:

0.00237

Gnomad OTH exome

AF:

0.00198

GnomAD4 exome

AF:

0.00171

AC:

2506

AN:

1461708

Hom.:

Cov.:

AF XY:

0.00172

AC XY:

1253

AN XY:

727136

show subpopulations

Gnomad4 AFR exome

AF:

0.000209

Gnomad4 AMR exome

AF:

0.000179

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000348

Gnomad4 FIN exome

AF:

0.00449

Gnomad4 NFE exome

AF:

0.00195

Gnomad4 OTH exome

AF:

0.00139

GnomAD4 genome

AF:

0.00146

AC:

222

AN:

152260

Hom.:

Cov.:

AF XY:

0.00146

AC XY:

109

AN XY:

74436

show subpopulations

Gnomad4 AFR

AF:

0.000217

Gnomad4 AMR

AF:

0.000458

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00321

Gnomad4 NFE

AF:

0.00246

Gnomad4 OTH

AF:

0.00237

Alfa

AF:

0.00207

Hom.:

Bravo

AF:

0.00112

TwinsUK

AF:

0.00243

AC:

ALSPAC

AF:

0.000778

AC:

ESP6500AA

AF:

0.000246

AC:

ESP6500EA

AF:

0.00227

AC:

ExAC

AF:

0.00160

AC:

194

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

Invitae

Jun 20, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.53

BayesDel_addAF

Benign

-0.13

BayesDel_noAF

Uncertain

0.040

Cadd

Uncertain

Dann

Uncertain

1.0

DEOGEN2

Benign

0.044

T;T

Eigen

Pathogenic

0.82

Eigen_PC

Pathogenic

0.82

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Uncertain

0.97

D;D

M_CAP

Uncertain

0.17

MetaRNN

Benign

0.10

T;T

MetaSVM

Uncertain

0.64

MutationAssessor

Uncertain

2.7

M;.

MutationTaster

Benign

1.0

D;D;D

PrimateAI

Uncertain

0.64

PROVEAN

Benign

-0.90

N;N

REVEL

Uncertain

0.57

Sift

Uncertain

0.014

D;D

Sift4G

Benign

0.077

T;T

Polyphen

0.99

D;.

Vest4

0.79

MVP

0.62

MPC

0.19

ClinPred

0.057

GERP RS

5.8

Varity_R

0.21

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