9-14737588-G-A
Variant summary
Our verdict is Benign. Variant got -7 ACMG points: 0P and 7B. BP4_StrongBP6_ModerateBP7
The NM_001379081.2(FREM1):c.6348C>T(p.Asn2116=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000122 in 1,557,576 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).
Frequency
Genomes: 𝑓 0.000013 ( 0 hom., cov: 33)
Exomes 𝑓: 0.000012 ( 0 hom. )
Consequence
FREM1
NM_001379081.2 synonymous
NM_001379081.2 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 1.44
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 -7 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.56).
BP6
?
Variant 9-14737588-G-A is Benign according to our data. Variant chr9-14737588-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 3046710.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
?
Synonymous conserved (PhyloP=1.44 with no splicing effect.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
FREM1 | NM_001379081.2 | c.6348C>T | p.Asn2116= | synonymous_variant | 37/37 | ENST00000380880.4 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
FREM1 | ENST00000380880.4 | c.6348C>T | p.Asn2116= | synonymous_variant | 37/37 | 5 | NM_001379081.2 | P1 | |
FREM1 | ENST00000380894.5 | c.1956C>T | p.Asn652= | synonymous_variant | 14/14 | 1 | |||
FREM1 | ENST00000380875.7 | c.*914C>T | 3_prime_UTR_variant, NMD_transcript_variant | 31/31 | 1 | ||||
FREM1 | ENST00000427623.5 | c.*529C>T | 3_prime_UTR_variant, NMD_transcript_variant | 11/11 | 5 |
Frequencies
GnomAD3 genomes ? AF: 0.0000131 AC: 2AN: 152120Hom.: 0 Cov.: 33
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GnomAD4 exome AF: 0.0000121 AC: 17AN: 1405456Hom.: 0 Cov.: 35 AF XY: 0.0000144 AC XY: 10AN XY: 695040
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ClinVar
Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
FREM1-related disorder Benign:1
Likely benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Mar 25, 2019 | 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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Benign
RBP_binding_hub_radar
RBP_regulation_power_radar
Splicing
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at