chr9-14737462-C-T
Variant summary
Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_ModerateBP6_Very_StrongBP7BS1
The NM_001379081.2(FREM1):c.6474G>A(p.Gly2158=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000206 in 1,613,794 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Genomes: 𝑓 0.00014 ( 0 hom., cov: 32)
Exomes 𝑓: 0.00021 ( 3 hom. )
Consequence
FREM1
NM_001379081.2 synonymous
NM_001379081.2 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 0.0470
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 Benign. Variant got -15 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.37).
BP6
?
Variant 9-14737462-C-T is Benign according to our data. Variant chr9-14737462-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 2711736.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr9-14737462-C-T is described in Lovd as [Likely_benign].
BP7
?
Synonymous conserved (PhyloP=0.047 with no splicing effect.
BS1
?
Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.000145 (22/152204) while in subpopulation SAS AF= 0.00457 (22/4812). AF 95% confidence interval is 0.00309. There are 0 homozygotes in gnomad4. There are 18 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
FREM1 | NM_001379081.2 | c.6474G>A | p.Gly2158= | synonymous_variant | 37/37 | ENST00000380880.4 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
FREM1 | ENST00000380880.4 | c.6474G>A | p.Gly2158= | synonymous_variant | 37/37 | 5 | NM_001379081.2 | P1 | |
FREM1 | ENST00000380894.5 | c.2082G>A | p.Gly694= | synonymous_variant | 14/14 | 1 | |||
FREM1 | ENST00000380875.7 | c.*1040G>A | 3_prime_UTR_variant, NMD_transcript_variant | 31/31 | 1 | ||||
FREM1 | ENST00000427623.5 | c.*655G>A | 3_prime_UTR_variant, NMD_transcript_variant | 11/11 | 5 |
Frequencies
GnomAD3 genomes ? AF: 0.000145 AC: 22AN: 152086Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.000365 AC: 91AN: 249006Hom.: 1 AF XY: 0.000533 AC XY: 72AN XY: 135104
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GnomAD4 exome AF: 0.000213 AC: 311AN: 1461590Hom.: 3 Cov.: 30 AF XY: 0.000301 AC XY: 219AN XY: 727064
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ClinVar
Significance: Benign/Likely benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not provided Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 26, 2024 | - - |
FREM1-related disorder Benign:1
Likely benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | May 01, 2023 | This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). - |
Computational scores
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BayesDel_noAF
Benign
Cadd
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Dann
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at