rs727505369
Variant summary
Our verdict is Likely pathogenic. Variant got 8 ACMG points: 8P and 0B. PM1PM2PP2PP3_ModeratePP5
The NM_023110.3(FGFR1):āc.821A>Gā(p.Glu274Gly) variant causes a missense change. The variant allele was found at a frequency of 0.000000684 in 1,461,710 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. E274Q) has been classified as Uncertain significance.
Frequency
Consequence
NM_023110.3 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_pathogenic. Variant got 8 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
FGFR1 | NM_023110.3 | c.821A>G | p.Glu274Gly | missense_variant | 7/18 | ENST00000447712.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
FGFR1 | ENST00000447712.7 | c.821A>G | p.Glu274Gly | missense_variant | 7/18 | 1 | NM_023110.3 | P4 | |
ENST00000528407.1 | n.388-1326T>C | intron_variant, non_coding_transcript_variant | 4 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD4 exome AF: 6.84e-7 AC: 1AN: 1461710Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1AN XY: 727122
GnomAD4 genome ? Cov.: 32
ClinVar
Submissions by phenotype
Hypogonadotropic hypogonadism 7 with or without anosmia Pathogenic:1
Likely pathogenic, criteria provided, single submitter | case-control | Chan Lab, Boston Children's Hospital | Nov 01, 2014 | - - |
Delayed puberty Pathogenic:1
Likely pathogenic, criteria provided, single submitter | case-control | Chan Lab, Boston Children's Hospital | Nov 01, 2014 | - - |
Pfeiffer syndrome;C0406612:Encephalocraniocutaneous lipomatosis;C0432122:Trigonocephaly 1;C0432283:Osteoglophonic dysplasia;C0795998:Jackson-Weiss syndrome;C1563720:Hypogonadotropic hypogonadism 2 with or without anosmia;C1845146:Hartsfield-Bixler-Demyer syndrome Pathogenic:1
Likely pathogenic, criteria provided, single submitter | clinical testing | Fulgent Genetics, Fulgent Genetics | Jul 18, 2021 | - - |
Hypogonadotropic hypogonadism 2 with or without anosmia Uncertain:1
Uncertain significance, criteria provided, single submitter | research | Reproductive Endocrine Unit, Massachusetts General Hospital | May 04, 2023 | The variant has been classified as VUS based on the variant meeting the following ACMG Criteria: PM2,PP3. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at