19-17762764-C-A
Variant names:
Variant summary
Our verdict is Benign. Variant got -9 ACMG points: 2P and 11B. PM2BP4_StrongBP6_ModerateBP7BS1
The NM_015122.3(FCHO1):c.30C>A(p.Gly10Gly) variant causes a splice region, synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000304 in 1,611,688 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (★). Synonymous variant affecting the same amino acid position (i.e. G10G) has been classified as Likely benign.
Frequency
Genomes: 𝑓 0.000066 ( 0 hom., cov: 31)
Exomes 𝑓: 0.000027 ( 0 hom. )
Consequence
FCHO1
NM_015122.3 splice_region, synonymous
NM_015122.3 splice_region, synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -2.51
Genes affected
FCHO1 (HGNC:29002): (FCH and mu domain containing endocytic adaptor 1) Enables AP-2 adaptor complex binding activity. Involved in clathrin coat assembly and clathrin-dependent endocytosis. Located in cytosol; nucleoplasm; and plasma membrane. Is active in clathrin-coated pit. Implicated in primary immunodeficiency disease. [provided by Alliance of Genome Resources, Apr 2022]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -9 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.71).
BP6
Variant 19-17762764-C-A is Benign according to our data. Variant chr19-17762764-C-A is described in ClinVar as [Likely_benign]. Clinvar id is 2065943.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
Synonymous conserved (PhyloP=-2.51 with no splicing effect.
BS1
Variant frequency is greater than expected in population amr. gnomad4_exome allele frequency = 0.0000267 (39/1459468) while in subpopulation AMR AF= 0.000246 (11/44724). AF 95% confidence interval is 0.000137. There are 0 homozygotes in gnomad4_exome. There are 22 alleles in male gnomad4_exome subpopulation. Median coverage is 30. This position pass quality control queck.
Transcripts
RefSeq
Ensembl
| Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
|---|---|---|---|---|---|---|---|---|---|---|
| FCHO1 | ENST00000699203.1 | c.-121C>A | splice_region_variant | Exon 3 of 22 | ENSP00000514201.1 | |||||
| FCHO1 | ENST00000596536.6 | c.30C>A | p.Gly10Gly | splice_region_variant, synonymous_variant | Exon 5 of 29 | 5 | NM_015122.3 | ENSP00000470731.1 | ||
| FCHO1 | ENST00000699212.1 | c.30C>A | p.Gly10Gly | splice_region_variant, synonymous_variant | Exon 5 of 30 | ENSP00000514208.1 | ||||
| FCHO1 | ENST00000594202.6 | c.30C>A | p.Gly10Gly | splice_region_variant, synonymous_variant | Exon 5 of 29 | 5 | ENSP00000473001.1 | |||
| FCHO1 | ENST00000596309.6 | c.30C>A | p.Gly10Gly | splice_region_variant, synonymous_variant | Exon 5 of 29 | 4 | ENSP00000470511.2 | |||
| FCHO1 | ENST00000596951.6 | c.30C>A | p.Gly10Gly | splice_region_variant, synonymous_variant | Exon 5 of 29 | 5 | ENSP00000472417.1 | |||
| FCHO1 | ENST00000600209.6 | c.30C>A | p.Gly10Gly | splice_region_variant, synonymous_variant | Exon 5 of 29 | 5 | ENSP00000469075.2 | |||
| FCHO1 | ENST00000600676.5 | c.30C>A | p.Gly10Gly | splice_region_variant, synonymous_variant | Exon 4 of 28 | 2 | ENSP00000470493.1 | |||
| FCHO1 | ENST00000699176.1 | c.30C>A | p.Gly10Gly | splice_region_variant, synonymous_variant | Exon 5 of 29 | ENSP00000514179.1 | ||||
| FCHO1 | ENST00000699177.1 | c.30C>A | p.Gly10Gly | splice_region_variant, synonymous_variant | Exon 5 of 29 | ENSP00000514180.1 | ||||
| FCHO1 | ENST00000699207.1 | c.30C>A | p.Gly10Gly | splice_region_variant, synonymous_variant | Exon 5 of 29 | ENSP00000514204.1 | ||||
| FCHO1 | ENST00000699209.1 | c.30C>A | p.Gly10Gly | splice_region_variant, synonymous_variant | Exon 5 of 29 | ENSP00000514206.1 | ||||
| FCHO1 | ENST00000699215.1 | c.30C>A | p.Gly10Gly | splice_region_variant, synonymous_variant | Exon 4 of 28 | ENSP00000514211.1 | ||||
| FCHO1 | ENST00000699202.1 | c.30C>A | p.Gly10Gly | splice_region_variant, synonymous_variant | Exon 5 of 29 | ENSP00000514200.1 | ||||
| FCHO1 | ENST00000699214.1 | c.30C>A | p.Gly10Gly | splice_region_variant, synonymous_variant | Exon 4 of 28 | ENSP00000514210.1 | ||||
| FCHO1 | ENST00000699208.1 | c.30C>A | p.Gly10Gly | splice_region_variant, synonymous_variant | Exon 5 of 28 | ENSP00000514205.1 | ||||
| FCHO1 | ENST00000699198.1 | c.30C>A | p.Gly10Gly | splice_region_variant, synonymous_variant | Exon 5 of 29 | ENSP00000514196.1 | ||||
| FCHO1 | ENST00000699199.1 | c.30C>A | p.Gly10Gly | splice_region_variant, synonymous_variant | Exon 4 of 28 | ENSP00000514197.1 | ||||
| FCHO1 | ENST00000699213.1 | c.30C>A | p.Gly10Gly | splice_region_variant, synonymous_variant | Exon 4 of 28 | ENSP00000514209.1 | ||||
| FCHO1 | ENST00000699197.1 | c.30C>A | p.Gly10Gly | splice_region_variant, synonymous_variant | Exon 5 of 28 | ENSP00000514195.1 | ||||
| FCHO1 | ENST00000699200.1 | c.30C>A | p.Gly10Gly | splice_region_variant, synonymous_variant | Exon 5 of 28 | ENSP00000514198.1 | ||||
| FCHO1 | ENST00000699196.1 | c.30C>A | p.Gly10Gly | splice_region_variant, synonymous_variant | Exon 5 of 27 | ENSP00000514194.1 | ||||
| FCHO1 | ENST00000699203 | c.-121C>A | 5_prime_UTR_variant | Exon 3 of 22 | ENSP00000514201.1 | |||||
| FCHO1 | ENST00000699201.1 | n.30C>A | splice_region_variant, non_coding_transcript_exon_variant | Exon 5 of 28 | ENSP00000514199.1 | |||||
| FCHO1 | ENST00000699205.1 | n.30C>A | splice_region_variant, non_coding_transcript_exon_variant | Exon 5 of 27 | ENSP00000514202.1 | |||||
| FCHO1 | ENST00000699206.1 | n.30C>A | splice_region_variant, non_coding_transcript_exon_variant | Exon 5 of 29 | ENSP00000514203.1 | |||||
| FCHO1 | ENST00000699210.1 | n.30C>A | splice_region_variant, non_coding_transcript_exon_variant | Exon 5 of 28 | ENSP00000514207.1 |
Frequencies
GnomAD3 genomes 0.0000657 AC: 10AN: 152102Hom.: 0 Cov.: 31
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GnomAD3 exomes AF: 0.0000716 AC: 18AN: 251454Hom.: 0 AF XY: 0.0000736 AC XY: 10AN XY: 135896
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GnomAD4 exome AF: 0.0000267 AC: 39AN: 1459468Hom.: 0 Cov.: 30 AF XY: 0.0000303 AC XY: 22AN XY: 726288
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GnomAD4 genome 0.0000657 AC: 10AN: 152220Hom.: 0 Cov.: 31 AF XY: 0.0000672 AC XY: 5AN XY: 74426
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ClinVar
Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not provided Benign:1
Nov 27, 2024
Labcorp Genetics (formerly Invitae), Labcorp
Significance: Likely benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing
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Computational scores
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Name
Calibrated prediction
Score
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BayesDel_noAF
Benign
CADD
Benign
DANN
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