Variant 9-14737256-AT-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -1 ACMG points: 0P and 1B. BS1_Supporting

The NM_001379081.2(FREM1):c.*139del variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00246 in 572,062 control chromosomes in the GnomAD database, including 3 homozygotes. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0020 ( 1 hom., cov: 32)

Exomes 𝑓: 0.0026 ( 2 hom. )

Consequence

FREM1
NM_001379081.2 3_prime_UTR

Scores

Not classified

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.125

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 Likely_benign. Variant got -1 ACMG points.

BS1

Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.00204 (310/152314) while in subpopulation SAS AF= 0.00435 (21/4828). AF 95% confidence interval is 0.00291. There are 1 homozygotes in gnomad4. There are 152 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck. Existence of Clinvar submissions makes me limit the strength of this signal to Supporting

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FREM1	NM_001379081.2 linkuse as main transcript	c.*139del		3_prime_UTR_variant	37/37	ENST00000380880.4

Ensembl

Gene	Transcript	HGVSc	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FREM1	ENST00000380880.4 linkuse as main transcript	c.*139del	3_prime_UTR_variant	37/37	5	NM_001379081.2	P1	Q5H8C1-1
FREM1	ENST00000380894.5 linkuse as main transcript	c.*139del	3_prime_UTR_variant	14/14	1			Q5H8C1-2
FREM1	ENST00000380875.7 linkuse as main transcript	c.*1245del	3_prime_UTR_variant, NMD_transcript_variant	31/31	1

Frequencies

GnomAD3 genomes

AF:

0.00204

AC:

310

AN:

152196

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000627

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000981

Gnomad ASJ

AF:

0.00606

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00435

Gnomad FIN

AF:

0.000377

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.00322

Gnomad OTH

AF:

0.00143

GnomAD4 exome

AF:

0.00262

AC:

1098

AN:

419748

Hom.:

Cov.:

AF XY:

0.00277

AC XY:

599

AN XY:

216588

show subpopulations

Gnomad4 AFR exome

AF:

0.000436

Gnomad4 AMR exome

AF:

0.00100

Gnomad4 ASJ exome

AF:

0.00716

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00370

Gnomad4 FIN exome

AF:

0.000485

Gnomad4 NFE exome

AF:

0.00302

Gnomad4 OTH exome

AF:

0.00273

GnomAD4 genome

AF:

0.00204

AC:

310

AN:

152314

Hom.:

Cov.:

AF XY:

0.00204

AC XY:

152

AN XY:

74478

show subpopulations

Gnomad4 AFR

AF:

0.000625

Gnomad4 AMR

AF:

0.000980

Gnomad4 ASJ

AF:

0.00606

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00435

Gnomad4 FIN

AF:

0.000377

Gnomad4 NFE

AF:

0.00322

Gnomad4 OTH

AF:

0.00142

Alfa

AF:

0.000163

Hom.:

Bravo

AF:

0.00203

Asia WGS

AF:

0.00260

AC:

AN:

3478

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Oculotrichoanal syndrome

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

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