GeneBe

chr19-17769819-T-C

Position:

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_015122.3(FCHO1):​c.337-606T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000658 in 151,918 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 33)

Consequence

FCHO1
NM_015122.3 intron

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.0380
Variant links:
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 Likely_benign. Variant got -2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.92).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
FCHO1NM_015122.3 linkuse as main transcriptc.337-606T>C intron_variant ENST00000596536.6 NP_055937.1 O14526-1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
FCHO1ENST00000596536.6 linkuse as main transcriptc.337-606T>C intron_variant 5 NM_015122.3 ENSP00000470731.1 O14526-1
FCHO1ENST00000699212.1 linkuse as main transcriptc.337-606T>C intron_variant ENSP00000514208.1 A0A8V8TPN1
FCHO1ENST00000594202.6 linkuse as main transcriptc.337-606T>C intron_variant 5 ENSP00000473001.1 A0A0C3SFZ9
FCHO1ENST00000596309.6 linkuse as main transcriptc.337-606T>C intron_variant 4 ENSP00000470511.2 O14526-1M0QZF0
FCHO1ENST00000596951.6 linkuse as main transcriptc.337-606T>C intron_variant 5 ENSP00000472417.1 O14526-1
FCHO1ENST00000600209.6 linkuse as main transcriptc.337-606T>C intron_variant 5 ENSP00000469075.2 O14526-1M0QXD1
FCHO1ENST00000600676.5 linkuse as main transcriptc.337-606T>C intron_variant 2 ENSP00000470493.1 O14526-1
FCHO1ENST00000699176.1 linkuse as main transcriptc.337-606T>C intron_variant ENSP00000514179.1 O14526-1
FCHO1ENST00000699177.1 linkuse as main transcriptc.337-606T>C intron_variant ENSP00000514180.1 O14526-1
FCHO1ENST00000699207.1 linkuse as main transcriptc.337-606T>C intron_variant ENSP00000514204.1 O14526-1
FCHO1ENST00000699209.1 linkuse as main transcriptc.337-606T>C intron_variant ENSP00000514206.1 O14526-1
FCHO1ENST00000699215.1 linkuse as main transcriptc.337-606T>C intron_variant ENSP00000514211.1 O14526-1
FCHO1ENST00000699202.1 linkuse as main transcriptc.337-645T>C intron_variant ENSP00000514200.1 A0A8V8TMX9
FCHO1ENST00000699214.1 linkuse as main transcriptc.337-645T>C intron_variant ENSP00000514210.1 A0A8V8TMX9
FCHO1ENST00000699208.1 linkuse as main transcriptc.337-606T>C intron_variant ENSP00000514205.1 A0A8V8TPA0
FCHO1ENST00000699198.1 linkuse as main transcriptc.337-606T>C intron_variant ENSP00000514196.1 M0QYA9
FCHO1ENST00000699199.1 linkuse as main transcriptc.337-606T>C intron_variant ENSP00000514197.1 M0QYA9
FCHO1ENST00000699213.1 linkuse as main transcriptc.337-606T>C intron_variant ENSP00000514209.1 M0QYA9
FCHO1ENST00000699197.1 linkuse as main transcriptc.337-606T>C intron_variant ENSP00000514195.1 A0A8V8TNC3
FCHO1ENST00000699200.1 linkuse as main transcriptc.337-606T>C intron_variant ENSP00000514198.1 A0A8V8TNC3
FCHO1ENST00000699196.1 linkuse as main transcriptc.337-606T>C intron_variant ENSP00000514194.1 A0A8V8TP91
FCHO1ENST00000699203.1 linkuse as main transcriptc.187-606T>C intron_variant ENSP00000514201.1 A0A8V8TPM7
FCHO1ENST00000699201.1 linkuse as main transcriptn.*213-606T>C intron_variant ENSP00000514199.1 A0A8V8TP96
FCHO1ENST00000699205.1 linkuse as main transcriptn.337-606T>C intron_variant ENSP00000514202.1 A0A8V8TMV7
FCHO1ENST00000699206.1 linkuse as main transcriptn.337-606T>C intron_variant ENSP00000514203.1 A0A8V8TMV7
FCHO1ENST00000699210.1 linkuse as main transcriptn.195-606T>C intron_variant ENSP00000514207.1 A0A8V8TND1

Frequencies

GnomAD3 genomes
AF:
0.00000658
AC:
1
AN:
151918
Hom.:
0
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.0000242
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00
Gnomad OTH
AF:
0.00
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome
AF:
0.00000658
AC:
1
AN:
151918
Hom.:
0
Cov.:
33
AF XY:
0.00
AC XY:
0
AN XY:
74182
show subpopulations
Gnomad4 AFR
AF:
0.0000242
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.92
CADD
Benign
4.1
DANN
Benign
0.57

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.0
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs4808095; hg19: chr19-17880628; API