Genetic Variant FCHO1:c.28-7C>T (chr19-17762755-C-T) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6_Moderate

The NM_015122.3(FCHO1):c.28-7C>T variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000344 in 1,454,430 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: not found (cov: 31)

Exomes 𝑓: 0.0000034 ( 0 hom. )

Consequence

FCHO1
NM_015122.3 splice_region, intron

Scores

Splicing: ADA: 0.00002463

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.264

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]

FCHO1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.81).

BP6

Variant 19-17762755-C-T is Benign according to our data. Variant chr19-17762755-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 3688755.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FCHO1	NM_015122.3 link	c.28-7C>T		splice_region_variant, intron_variant	Intron 4 of 28	ENST00000596536.6	NP_055937.1	O14526-1

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
FCHO1	ENST00000596536.6 link	c.28-7C>T	splice_region_variant, intron_variant	Intron 4 of 28	5	NM_015122.3	ENSP00000470731.1	O14526-1
FCHO1	ENST00000699212.1 link	c.28-7C>T	splice_region_variant, intron_variant	Intron 4 of 29			ENSP00000514208.1	A0A8V8TPN1
FCHO1	ENST00000594202.6 link	c.28-7C>T	splice_region_variant, intron_variant	Intron 4 of 28	5		ENSP00000473001.1	A0A0C3SFZ9
FCHO1	ENST00000596309.6 link	c.28-7C>T	splice_region_variant, intron_variant	Intron 4 of 28	4		ENSP00000470511.2	O14526-1M0QZF0
FCHO1	ENST00000596951.6 link	c.28-7C>T	splice_region_variant, intron_variant	Intron 4 of 28	5		ENSP00000472417.1	O14526-1
FCHO1	ENST00000600209.6 link	c.28-7C>T	splice_region_variant, intron_variant	Intron 4 of 28	5		ENSP00000469075.2	O14526-1M0QXD1
FCHO1	ENST00000600676.5 link	c.28-7C>T	splice_region_variant, intron_variant	Intron 3 of 27	2		ENSP00000470493.1	O14526-1
FCHO1	ENST00000699176.1 link	c.28-7C>T	splice_region_variant, intron_variant	Intron 4 of 28			ENSP00000514179.1	O14526-1
FCHO1	ENST00000699177.1 link	c.28-7C>T	splice_region_variant, intron_variant	Intron 4 of 28			ENSP00000514180.1	O14526-1
FCHO1	ENST00000699207.1 link	c.28-7C>T	splice_region_variant, intron_variant	Intron 4 of 28			ENSP00000514204.1	O14526-1
FCHO1	ENST00000699209.1 link	c.28-7C>T	splice_region_variant, intron_variant	Intron 4 of 28			ENSP00000514206.1	O14526-1
FCHO1	ENST00000699215.1 link	c.28-7C>T	splice_region_variant, intron_variant	Intron 3 of 27			ENSP00000514211.1	O14526-1
FCHO1	ENST00000699202.1 link	c.28-7C>T	splice_region_variant, intron_variant	Intron 4 of 28			ENSP00000514200.1	A0A8V8TMX9
FCHO1	ENST00000699214.1 link	c.28-7C>T	splice_region_variant, intron_variant	Intron 3 of 27			ENSP00000514210.1	A0A8V8TMX9
FCHO1	ENST00000699208.1 link	c.28-7C>T	splice_region_variant, intron_variant	Intron 4 of 27			ENSP00000514205.1	A0A8V8TPA0
FCHO1	ENST00000699198.1 link	c.28-7C>T	splice_region_variant, intron_variant	Intron 4 of 28			ENSP00000514196.1	M0QYA9
FCHO1	ENST00000699199.1 link	c.28-7C>T	splice_region_variant, intron_variant	Intron 3 of 27			ENSP00000514197.1	M0QYA9
FCHO1	ENST00000699213.1 link	c.28-7C>T	splice_region_variant, intron_variant	Intron 3 of 27			ENSP00000514209.1	M0QYA9
FCHO1	ENST00000699197.1 link	c.28-7C>T	splice_region_variant, intron_variant	Intron 4 of 27			ENSP00000514195.1	A0A8V8TNC3
FCHO1	ENST00000699200.1 link	c.28-7C>T	splice_region_variant, intron_variant	Intron 4 of 27			ENSP00000514198.1	A0A8V8TNC3
FCHO1	ENST00000699196.1 link	c.28-7C>T	splice_region_variant, intron_variant	Intron 4 of 26			ENSP00000514194.1	A0A8V8TP91
FCHO1	ENST00000699203.1 link	c.-123-7C>T	splice_region_variant, intron_variant	Intron 2 of 21			ENSP00000514201.1	A0A8V8TPM7
FCHO1	ENST00000699201.1 link	n.28-7C>T	splice_region_variant, intron_variant	Intron 4 of 27			ENSP00000514199.1	A0A8V8TP96
FCHO1	ENST00000699205.1 link	n.28-7C>T	splice_region_variant, intron_variant	Intron 4 of 26			ENSP00000514202.1	A0A8V8TMV7
FCHO1	ENST00000699206.1 link	n.28-7C>T	splice_region_variant, intron_variant	Intron 4 of 28			ENSP00000514203.1	A0A8V8TMV7
FCHO1	ENST00000699210.1 link	n.28-7C>T	splice_region_variant, intron_variant	Intron 4 of 27			ENSP00000514207.1	A0A8V8TND1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000398

AC:

AN:

251450

Hom.:

AF XY:

0.00000736

AC XY:

AN XY:

135896

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000879

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000344

AC:

AN:

1454430

Hom.:

Cov.:

AF XY:

0.00000276

AC XY:

AN XY:

724144

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000452

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

EpiCase

AF:

0.0000545

EpiControl

AF:

0.00

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Aug 07, 2024

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.81

CADD

Benign

3.6

DANN

Benign

0.85

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000025

dbscSNV1_RF

Benign

0.0040

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over