Variant chr6-75312455-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2

The NM_015687.5(FILIP1):c.3377C>T(p.Thr1126Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00276 in 1,614,112 control chromosomes in the GnomAD database, including 28 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0069 ( 9 hom., cov: 32)

Exomes 𝑓: 0.0023 ( 19 hom. )

Consequence

FILIP1
NM_015687.5 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 3.42

Variant links:

Genes affected

FILIP1 (HGNC:21015): (filamin A interacting protein 1) This gene encodes a filamin A binding protein. The encoded protein promotes the degradation of filamin A and may regulate cortical neuron migration and dendritic spine morphology. Mice lacking a functional copy of this gene exhibit reduced dendritic spine length and altered excitatory signaling. [provided by RefSeq, Oct 2016]

FILIP1 links:

TMEM30A-DT (HGNC:48985): (TMEM30A divergent transcript)

TMEM30A-DT links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0085476935).

BP6

Variant 6-75312455-G-A is Benign according to our data. Variant chr6-75312455-G-A is described in ClinVar as [Benign]. Clinvar id is 718440.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population afr. gnomad4_exome allele frequency = 0.00233 (3405/1461892) while in subpopulation AFR AF= 0.0179 (599/33480). AF 95% confidence interval is 0.0167. There are 19 homozygotes in gnomad4_exome. There are 1675 alleles in male gnomad4_exome subpopulation. Median coverage is 35. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 9 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FILIP1	NM_015687.5 linkuse as main transcript	c.3377C>T	p.Thr1126Met	missense_variant	5/6	ENST00000237172.12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FILIP1	ENST00000237172.12 linkuse as main transcript	c.3377C>T	p.Thr1126Met	missense_variant	5/6	1	NM_015687.5	P4	Q7Z7B0-1
TMEM30A-DT	ENST00000661161.1 linkuse as main transcript	n.384G>A		non_coding_transcript_exon_variant	2/2

Frequencies

GnomAD3 genomes

AF:

0.00685

AC:

1042

AN:

152102

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0155

Gnomad AMI

AF:

0.00548

Gnomad AMR

AF:

0.0130

Gnomad ASJ

AF:

0.0101

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000621

Gnomad FIN

AF:

0.000189

Gnomad MID

AF:

0.0190

Gnomad NFE

AF:

0.00182

Gnomad OTH

AF:

0.0125

GnomAD3 exomes

AF:

0.00355

AC:

893

AN:

251396

Hom.:

AF XY:

0.00326

AC XY:

443

AN XY:

135866

show subpopulations

Gnomad AFR exome

AF:

0.0157

Gnomad AMR exome

AF:

0.00607

Gnomad ASJ exome

AF:

0.00873

Gnomad EAS exome

AF:

0.0000544

Gnomad SAS exome

AF:

0.000588

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00249

Gnomad OTH exome

AF:

0.00603

GnomAD4 exome

AF:

0.00233

AC:

3405

AN:

1461892

Hom.:

Cov.:

AF XY:

0.00230

AC XY:

1675

AN XY:

727248

show subpopulations

Gnomad4 AFR exome

AF:

0.0179

Gnomad4 AMR exome

AF:

0.00693

Gnomad4 ASJ exome

AF:

0.00972

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.000742

Gnomad4 FIN exome

AF:

0.0000374

Gnomad4 NFE exome

AF:

0.00156

Gnomad4 OTH exome

AF:

0.00571

GnomAD4 genome

AF:

0.00687

AC:

1046

AN:

152220

Hom.:

Cov.:

AF XY:

0.00716

AC XY:

533

AN XY:

74412

show subpopulations

Gnomad4 AFR

AF:

0.0156

Gnomad4 AMR

AF:

0.0130

Gnomad4 ASJ

AF:

0.0101

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000622

Gnomad4 FIN

AF:

0.000189

Gnomad4 NFE

AF:

0.00181

Gnomad4 OTH

AF:

0.0123

Alfa

AF:

0.00318

Hom.:

Bravo

AF:

0.00814

TwinsUK

AF:

0.00135

AC:

ALSPAC

AF:

0.00234

AC:

ESP6500AA

AF:

0.0113

AC:

ESP6500EA

AF:

0.00244

AC:

ExAC

AF:

0.00343

AC:

416

Asia WGS

AF:

0.00260

AC:

AN:

3478

EpiCase

AF:

0.00278

EpiControl

AF:

0.00362

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Dec 20, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.13

BayesDel_addAF

Benign

-0.46

BayesDel_noAF

Benign

-0.42

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.20

.;T;T

Eigen

Uncertain

0.31

Eigen_PC

Uncertain

0.37

FATHMM_MKL

Uncertain

0.96

LIST_S2

Uncertain

0.86

D;D;D

MetaRNN

Benign

0.0085

T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.9

L;L;.

MutationTaster

Benign

1.0

D;D;D

PrimateAI

Benign

0.43

PROVEAN

Uncertain

-3.8

D;D;D

REVEL

Benign

0.17

Sift

Benign

0.054

T;T;T

Sift4G

Uncertain

0.046

D;T;T

Polyphen

0.91

P;P;.

Vest4

0.25

MVP

0.66

MPC

0.34

ClinPred

0.048

GERP RS

5.8

Varity_R

0.095

gMVP

0.65

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