Variant chr9-14740218-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 1P and 1B. PP5BP4

The NM_001379081.2(FREM1):c.6271G>A(p.Val2091Ile) variant causes a missense change. The variant allele was found at a frequency of 0.00000548 in 1,460,434 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Pathogenic (no stars).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000055 ( 0 hom. )

Consequence

FREM1
NM_001379081.2 missense

Scores

Clinical Significance

Pathogenic no assertion criteria provided P:1O:1

Conservation

PhyloP100: 4.10

Variant links:

Genes affected

FREM1 (HGNC:23399): (FRAS1 related extracellular matrix 1) This gene encodes a basement membrane protein that may play a role in craniofacial and renal development. Mutations in this gene have been associated with bifid nose with or without anorectal and renal anomalies. Alternatively spliced transcript variants encoding different isoforms have been described. PubMed ID 19940113 describes one such variant that initiates transcription within a distinct, internal exon; the resulting shorter isoform (named Toll-like/interleukin-1 receptor regulator, TILRR) is suggested to be a co-receptor of the interleukin 1 receptor family and may regulate receptor function and Toll-like receptor/interleukin 1 receptor signal transduction, contributing to the control of inflammatory response activation. [provided by RefSeq, Apr 2011]

FREM1 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PP5

Variant 9-14740218-C-T is Pathogenic according to our data. Variant chr9-14740218-C-T is described in ClinVar as [Pathogenic]. Clinvar id is 68751.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr9-14740218-C-T is described in Lovd as [Pathogenic].

BP4

Computational evidence support a benign effect (MetaRNN=0.38209608). . Strength limited to SUPPORTING due to the PP5.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FREM1	NM_001379081.2 linkuse as main transcript	c.6271G>A	p.Val2091Ile	missense_variant	36/37	ENST00000380880.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FREM1	ENST00000380880.4 linkuse as main transcript	c.6271G>A	p.Val2091Ile	missense_variant	36/37	5	NM_001379081.2	P1	Q5H8C1-1
FREM1	ENST00000380894.5 linkuse as main transcript	c.1879G>A	p.Val627Ile	missense_variant	13/14	1			Q5H8C1-2
FREM1	ENST00000380875.7 linkuse as main transcript	c.*837G>A		3_prime_UTR_variant, NMD_transcript_variant	30/31	1
FREM1	ENST00000427623.5 linkuse as main transcript	c.*452G>A		3_prime_UTR_variant, NMD_transcript_variant	10/11	5			Q5H8C1-4

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000403

AC:

AN:

248340

Hom.:

AF XY:

0.00000742

AC XY:

AN XY:

134768

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:

0.00000887

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000548

AC:

AN:

1460434

Hom.:

Cov.:

AF XY:

0.00000275

AC XY:

AN XY:

726502

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:

0.00000720

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ExAC

AF:

0.00000827

AC:

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:1Other:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

Oculotrichoanal syndrome

Pathogenic:1

Pathogenic, no assertion criteria provided

literature only

OMIM

Jun 01, 2011

- -

not provided

Other:1

not provided, no classification provided

literature only

UniProtKB/Swiss-Prot

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.16

BayesDel_addAF

Benign

-0.19

BayesDel_noAF

Benign

-0.51

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.13

T;.;T

Eigen

Uncertain

0.48

Eigen_PC

Uncertain

0.47

FATHMM_MKL

Uncertain

0.90

LIST_S2

Benign

0.73

T;T;.

M_CAP

Benign

0.014

MetaRNN

Benign

0.38

T;T;T

MetaSVM

Benign

-0.77

MutationAssessor

Uncertain

2.6

M;.;M

MutationTaster

Benign

0.65

D;D;D;D

PrimateAI

Benign

0.34

PROVEAN

Benign

-0.73

N;N;N

REVEL

Benign

0.14

Sift

Benign

0.14

T;T;T

Sift4G

Benign

0.16

T;T;T

Polyphen

0.84

P;.;P

Vest4

0.34

MutPred

0.57

Loss of sheet (P = 0.1158);.;Loss of sheet (P = 0.1158);

MVP

0.24

ClinPred

0.73

GERP RS

5.8

Varity_R

0.19

gMVP

0.57

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.070

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