rs2818940

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001379081.2(FREM1):c.829-12A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.796 in 1,590,922 control chromosomes in the GnomAD database, including 507,722 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.74 ( 42656 hom., cov: 31)

Exomes 𝑓: 0.80 ( 465066 hom. )

Consequence

FREM1
NM_001379081.2 intron

Scores

Splicing: ADA: 0.00001803

Clinical Significance

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

Conservation

PhyloP100: -0.0320

Publications

13 publications found

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 Gene-Disease associations (from GenCC):

oculotrichoanal syndrome
Inheritance: AR Classification: DEFINITIVE, STRONG, MODERATE, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), Orphanet, Ambry Genetics, G2P
BNAR syndrome
Inheritance: AR Classification: STRONG, SUPPORTIVE Submitted by: Orphanet, Labcorp Genetics (formerly Invitae)
isolated trigonocephaly
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
renal agenesis, unilateral
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
trigonocephaly 2
Inheritance: AD Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics

FREM1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.81).

BP6

Variant 9-14851619-T-C is Benign according to our data. Variant chr9-14851619-T-C is described in ClinVar as Benign. ClinVar VariationId is 262546.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.94 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001379081.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
FREM1	NM_001379081.2	MANE Select	c.829-12A>G	intron	N/A	NP_001366010.1	Q5H8C1-1
FREM1	NM_144966.7		c.829-12A>G	intron	N/A	NP_659403.4
FREM1	NM_001370060.1		c.856-12A>G	intron	N/A	NP_001356989.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
FREM1	ENST00000380880.4	TSL:5 MANE Select	c.829-12A>G	intron	N/A	ENSP00000370262.3	Q5H8C1-1
FREM1	ENST00000380875.7	TSL:1	n.829-12A>G	intron	N/A	ENSP00000370257.3	F8WE85
FREM1	ENST00000895028.1		c.829-12A>G	intron	N/A	ENSP00000565087.1

Frequencies

GnomAD3 genomes

AF:

0.739

AC:

112241

AN:

151930

Hom.:

42632

Cov.:

show subpopulations

Gnomad AFR

AF:

0.545

Gnomad AMI

AF:

0.654

Gnomad AMR

AF:

0.778

Gnomad ASJ

AF:

0.823

Gnomad EAS

AF:

0.962

Gnomad SAS

AF:

0.861

Gnomad FIN

AF:

0.869

Gnomad MID

AF:

0.747

Gnomad NFE

AF:

0.798

Gnomad OTH

AF:

0.757

GnomAD2 exomes

AF:

0.809

AC:

200598

AN:

247918

AF XY:

0.815

show subpopulations

Gnomad AFR exome

AF:

0.533

Gnomad AMR exome

AF:

0.798

Gnomad ASJ exome

AF:

0.825

Gnomad EAS exome

AF:

0.965

Gnomad FIN exome

AF:

0.863

Gnomad NFE exome

AF:

0.798

Gnomad OTH exome

AF:

0.801

GnomAD4 exome

AF:

0.802

AC:

1154022

AN:

1438874

Hom.:

465066

Cov.:

AF XY:

0.805

AC XY:

577443

AN XY:

717470

show subpopulations

African (AFR)

AF:

0.544

AC:

17884

AN:

32872

American (AMR)

AF:

0.797

AC:

35599

AN:

44690

Ashkenazi Jewish (ASJ)

AF:

0.826

AC:

21473

AN:

26008

East Asian (EAS)

AF:

0.964

AC:

38163

AN:

39580

South Asian (SAS)

AF:

0.867

AC:

74438

AN:

85836

European-Finnish (FIN)

AF:

0.860

AC:

45849

AN:

53342

Middle Eastern (MID)

AF:

0.717

AC:

4096

AN:

5716

European-Non Finnish (NFE)

AF:

0.796

AC:

868844

AN:

1091182

Other (OTH)

AF:

0.799

AC:

47676

AN:

59648

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.490

Heterozygous variant carriers

10869

21737

32606

43474

54343

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

20214

40428

60642

80856

101070

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.739

AC:

112314

AN:

152048

Hom.:

42656

Cov.:

AF XY:

0.747

AC XY:

55511

AN XY:

74352

show subpopulations

African (AFR)

AF:

0.545

AC:

22563

AN:

41408

American (AMR)

AF:

0.778

AC:

11875

AN:

15270

Ashkenazi Jewish (ASJ)

AF:

0.823

AC:

2855

AN:

3468

East Asian (EAS)

AF:

0.962

AC:

4975

AN:

5172

South Asian (SAS)

AF:

0.862

AC:

4154

AN:

4820

European-Finnish (FIN)

AF:

0.869

AC:

9203

AN:

10590

Middle Eastern (MID)

AF:

0.735

AC:

216

AN:

294

European-Non Finnish (NFE)

AF:

0.798

AC:

54274

AN:

68006

Other (OTH)

AF:

0.760

AC:

1604

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

Heterozygous variant carriers

1377

2754

4131

5508

6885

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

846

1692

2538

3384

4230

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.778

Hom.:

68533

Bravo

AF:

0.722

Asia WGS

AF:

0.872

AC:

3036

AN:

3478

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (3)

not specified (3)

Oculotrichoanal syndrome (2)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.81

CADD

Benign

(source)

DANN

Benign

0.44

PhyloP100

-0.032

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000018

dbscSNV1_RF

Benign

0.018

SpliceAI score (max)

0.13

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over