chr19-17762730-C-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2

The NM_015122.3(FCHO1):​c.28-32C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00548 in 1,503,916 control chromosomes in the GnomAD database, including 39 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0032 ( 1 hom., cov: 31)
Exomes 𝑓: 0.0057 ( 38 hom. )

Consequence

FCHO1
NM_015122.3 intron

Scores

9

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.140
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=0.0048695803).
BP6
Variant 19-17762730-C-T is Benign according to our data. Variant chr19-17762730-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 2649554.Status of the report is criteria_provided_single_submitter, 1 stars.
BS1
Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.00317 (483/152280) while in subpopulation NFE AF= 0.00545 (371/68026). AF 95% confidence interval is 0.005. There are 1 homozygotes in gnomad4. There are 214 alleles in male gnomad4 subpopulation. Median coverage is 31. This position pass quality control queck.
BS2
High Homozygotes in GnomAdExome4 at 38 AR gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
FCHO1NM_015122.3 linkuse as main transcriptc.28-32C>T 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.28-32C>T intron_variant 5 NM_015122.3 ENSP00000470731.1 O14526-1
FCHO1ENST00000699212.1 linkuse as main transcriptc.28-32C>T intron_variant ENSP00000514208.1 A0A8V8TPN1
FCHO1ENST00000594202.6 linkuse as main transcriptc.28-32C>T intron_variant 5 ENSP00000473001.1 A0A0C3SFZ9
FCHO1ENST00000596309.6 linkuse as main transcriptc.28-32C>T intron_variant 4 ENSP00000470511.2 O14526-1M0QZF0
FCHO1ENST00000596951.6 linkuse as main transcriptc.28-32C>T intron_variant 5 ENSP00000472417.1 O14526-1
FCHO1ENST00000600209.6 linkuse as main transcriptc.28-32C>T intron_variant 5 ENSP00000469075.2 O14526-1M0QXD1
FCHO1ENST00000600676.5 linkuse as main transcriptc.28-32C>T intron_variant 2 ENSP00000470493.1 O14526-1
FCHO1ENST00000699176.1 linkuse as main transcriptc.28-32C>T intron_variant ENSP00000514179.1 O14526-1
FCHO1ENST00000699177.1 linkuse as main transcriptc.28-32C>T intron_variant ENSP00000514180.1 O14526-1
FCHO1ENST00000699207.1 linkuse as main transcriptc.28-32C>T intron_variant ENSP00000514204.1 O14526-1
FCHO1ENST00000699209.1 linkuse as main transcriptc.28-32C>T intron_variant ENSP00000514206.1 O14526-1
FCHO1ENST00000699215.1 linkuse as main transcriptc.28-32C>T intron_variant ENSP00000514211.1 O14526-1
FCHO1ENST00000699202.1 linkuse as main transcriptc.28-32C>T intron_variant ENSP00000514200.1 A0A8V8TMX9
FCHO1ENST00000699214.1 linkuse as main transcriptc.28-32C>T intron_variant ENSP00000514210.1 A0A8V8TMX9
FCHO1ENST00000699208.1 linkuse as main transcriptc.28-32C>T intron_variant ENSP00000514205.1 A0A8V8TPA0
FCHO1ENST00000699198.1 linkuse as main transcriptc.28-32C>T intron_variant ENSP00000514196.1 M0QYA9
FCHO1ENST00000699199.1 linkuse as main transcriptc.28-32C>T intron_variant ENSP00000514197.1 M0QYA9
FCHO1ENST00000699213.1 linkuse as main transcriptc.28-32C>T intron_variant ENSP00000514209.1 M0QYA9
FCHO1ENST00000699197.1 linkuse as main transcriptc.28-32C>T intron_variant ENSP00000514195.1 A0A8V8TNC3
FCHO1ENST00000699200.1 linkuse as main transcriptc.28-32C>T intron_variant ENSP00000514198.1 A0A8V8TNC3
FCHO1ENST00000699196.1 linkuse as main transcriptc.28-32C>T intron_variant ENSP00000514194.1 A0A8V8TP91
FCHO1ENST00000699203.1 linkuse as main transcriptc.-123-32C>T intron_variant ENSP00000514201.1 A0A8V8TPM7
FCHO1ENST00000699201.1 linkuse as main transcriptn.28-32C>T intron_variant ENSP00000514199.1 A0A8V8TP96
FCHO1ENST00000699205.1 linkuse as main transcriptn.28-32C>T intron_variant ENSP00000514202.1 A0A8V8TMV7
FCHO1ENST00000699206.1 linkuse as main transcriptn.28-32C>T intron_variant ENSP00000514203.1 A0A8V8TMV7
FCHO1ENST00000699210.1 linkuse as main transcriptn.28-32C>T intron_variant ENSP00000514207.1 A0A8V8TND1

Frequencies

GnomAD3 genomes
AF:
0.00317
AC:
483
AN:
152162
Hom.:
1
Cov.:
31
show subpopulations
Gnomad AFR
AF:
0.000965
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00236
Gnomad ASJ
AF:
0.00374
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00331
Gnomad FIN
AF:
0.000188
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00545
Gnomad OTH
AF:
0.00239
GnomAD3 exomes
AF:
0.00354
AC:
891
AN:
251360
Hom.:
6
AF XY:
0.00379
AC XY:
515
AN XY:
135848
show subpopulations
Gnomad AFR exome
AF:
0.00105
Gnomad AMR exome
AF:
0.00217
Gnomad ASJ exome
AF:
0.00357
Gnomad EAS exome
AF:
0.0000544
Gnomad SAS exome
AF:
0.00369
Gnomad FIN exome
AF:
0.000231
Gnomad NFE exome
AF:
0.00546
Gnomad OTH exome
AF:
0.00375
GnomAD4 exome
AF:
0.00574
AC:
7758
AN:
1351636
Hom.:
38
Cov.:
22
AF XY:
0.00578
AC XY:
3926
AN XY:
678988
show subpopulations
Gnomad4 AFR exome
AF:
0.00105
Gnomad4 AMR exome
AF:
0.00211
Gnomad4 ASJ exome
AF:
0.00400
Gnomad4 EAS exome
AF:
0.0000256
Gnomad4 SAS exome
AF:
0.00350
Gnomad4 FIN exome
AF:
0.000487
Gnomad4 NFE exome
AF:
0.00679
Gnomad4 OTH exome
AF:
0.00566
GnomAD4 genome
AF:
0.00317
AC:
483
AN:
152280
Hom.:
1
Cov.:
31
AF XY:
0.00287
AC XY:
214
AN XY:
74450
show subpopulations
Gnomad4 AFR
AF:
0.000963
Gnomad4 AMR
AF:
0.00236
Gnomad4 ASJ
AF:
0.00374
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00332
Gnomad4 FIN
AF:
0.000188
Gnomad4 NFE
AF:
0.00545
Gnomad4 OTH
AF:
0.00236
Alfa
AF:
0.00437
Hom.:
0
Bravo
AF:
0.00361
TwinsUK
AF:
0.00458
AC:
17
ALSPAC
AF:
0.00571
AC:
22
ESP6500AA
AF:
0.00136
AC:
6
ESP6500EA
AF:
0.00581
AC:
50
ExAC
AF:
0.00355
AC:
431
Asia WGS
AF:
0.000866
AC:
3
AN:
3478
EpiCase
AF:
0.00725
EpiControl
AF:
0.00658

ClinVar

Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not provided Benign:1
Likely benign, criteria provided, single submitterclinical testingCeGaT Center for Human Genetics TuebingenJan 01, 2023FCHO1: BS2 -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_addAF
Benign
-0.48
T
BayesDel_noAF
Benign
-0.46
CADD
Benign
0.90
DANN
Benign
0.79
FATHMM_MKL
Benign
0.014
N
LIST_S2
Benign
0.35
T
M_CAP
Benign
0.00066
T
MetaRNN
Benign
0.0049
T
Sift4G
Benign
0.44
T
Vest4
0.13
MVP
0.35
GERP RS
0.84
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
2.1

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: rs117245024; hg19: chr19-17873539; API