9-14737256-AT-A
Variant names:
Variant summary
Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BS1_SupportingBS2
The NM_001379081.2(FREM1):c.*139delA 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
NM_001379081.2 3_prime_UTR
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 0.125
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]
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ACMG classification
Classification made for transcript
Verdict is Likely_benign. Variant got -5 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
BS2
High Homozygotes in GnomAdExome4 at 2 AD,AR gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
FREM1 | NM_001379081.2 | c.*139delA | 3_prime_UTR_variant | Exon 37 of 37 | ENST00000380880.4 | NP_001366010.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
FREM1 | ENST00000380880 | c.*139delA | 3_prime_UTR_variant | Exon 37 of 37 | 5 | NM_001379081.2 | ENSP00000370262.3 | |||
FREM1 | ENST00000380894 | c.*139delA | 3_prime_UTR_variant | Exon 14 of 14 | 1 | ENSP00000370278.1 | ||||
FREM1 | ENST00000380875.7 | n.*1245delA | non_coding_transcript_exon_variant | Exon 31 of 31 | 1 | ENSP00000370257.3 | ||||
FREM1 | ENST00000380875.7 | n.*1245delA | 3_prime_UTR_variant | Exon 31 of 31 | 1 | ENSP00000370257.3 |
Frequencies
GnomAD3 genomes AF: 0.00204 AC: 310AN: 152196Hom.: 1 Cov.: 32
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GnomAD4 exome AF: 0.00262 AC: 1098AN: 419748Hom.: 2 Cov.: 5 AF XY: 0.00277 AC XY: 599AN XY: 216588
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GnomAD4 genome AF: 0.00204 AC: 310AN: 152314Hom.: 1 Cov.: 32 AF XY: 0.00204 AC XY: 152AN XY: 74478
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
Oculotrichoanal syndrome Uncertain:1
Jun 14, 2016
Illumina Laboratory Services, Illumina
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing
- -
not provided Uncertain:1
-
Breakthrough Genomics, Breakthrough Genomics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: not provided
- -
Computational scores
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at