9-14775855-A-G

Variant names:

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_001379081.2(FREM1):c.4791T>C(p.Asp1597Asp) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.873 in 1,613,082 control chromosomes in the GnomAD database, including 615,881 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.86 ( 55966 hom., cov: 32)

Exomes 𝑓: 0.88 ( 559915 hom. )

Consequence

FREM1
NM_001379081.2 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:8

Conservation

PhyloP100: -0.0120

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.84).

BP6

Variant 9-14775855-A-G is Benign according to our data. Variant chr9-14775855-A-G is described in ClinVar as [Benign]. Clinvar id is 262542.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr9-14775855-A-G is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=-0.012 with no splicing effect.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.876 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FREM1	NM_001379081.2 link	c.4791T>C	p.Asp1597Asp	synonymous_variant	Exon 25 of 37	ENST00000380880.4	NP_001366010.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FREM1	ENST00000380880.4 link	c.4791T>C	p.Asp1597Asp	synonymous_variant	Exon 25 of 37	5	NM_001379081.2	ENSP00000370262.3		Q5H8C1-1

Frequencies

GnomAD3 genomes

AF:

0.857

AC:

130176

AN:

151914

Hom.:

55942

Cov.:

show subpopulations

Gnomad AFR

AF:

0.795

Gnomad AMI

AF:

0.683

Gnomad AMR

AF:

0.875

Gnomad ASJ

AF:

0.893

Gnomad EAS

AF:

0.858

Gnomad SAS

AF:

0.857

Gnomad FIN

AF:

0.910

Gnomad MID

AF:

0.883

Gnomad NFE

AF:

0.882

Gnomad OTH

AF:

0.872

GnomAD3 exomes

AF:

0.870

AC:

216627

AN:

249084

Hom.:

94283

AF XY:

0.872

AC XY:

117889

AN XY:

135126

show subpopulations

Gnomad AFR exome

AF:

0.796

Gnomad AMR exome

AF:

0.834

Gnomad ASJ exome

AF:

0.897

Gnomad EAS exome

AF:

0.870

Gnomad SAS exome

AF:

0.866

Gnomad FIN exome

AF:

0.910

Gnomad NFE exome

AF:

0.881

Gnomad OTH exome

AF:

0.869

GnomAD4 exome

AF:

0.875

AC:

1278506

AN:

1461050

Hom.:

559915

Cov.:

AF XY:

0.876

AC XY:

636352

AN XY:

726838

show subpopulations

Gnomad4 AFR exome

AF:

0.799

Gnomad4 AMR exome

AF:

0.838

Gnomad4 ASJ exome

AF:

0.894

Gnomad4 EAS exome

AF:

0.842

Gnomad4 SAS exome

AF:

0.867

Gnomad4 FIN exome

AF:

0.907

Gnomad4 NFE exome

AF:

0.879

Gnomad4 OTH exome

AF:

0.871

GnomAD4 genome

AF:

0.857

AC:

130253

AN:

152032

Hom.:

55966

Cov.:

AF XY:

0.858

AC XY:

63786

AN XY:

74328

show subpopulations

Gnomad4 AFR

AF:

0.795

Gnomad4 AMR

AF:

0.875

Gnomad4 ASJ

AF:

0.893

Gnomad4 EAS

AF:

0.857

Gnomad4 SAS

AF:

0.857

Gnomad4 FIN

AF:

0.910

Gnomad4 NFE

AF:

0.882

Gnomad4 OTH

AF:

0.866

Alfa

AF:

0.879

Hom.:

82734

Bravo

AF:

0.851

Asia WGS

AF:

0.803

AC:

2793

AN:

3478

EpiCase

AF:

0.879

EpiControl

AF:

0.882

ClinVar

Significance: Benign

Submissions summary: Benign:8

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:3

Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Genome Diagnostics Laboratory, University Medical Center Utrecht

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not provided

Benign:3

Apr 28, 2020

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Oculotrichoanal syndrome

Benign:2

Aug 10, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Jan 13, 2018

Illumina Laboratory Services, Illumina

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.84

CADD

Benign

1.8

DANN

Benign

0.34

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

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