19-17762758-G-T

Position:

• chr19-17762758-G-T

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2 BP4_Strong BP6_Moderate

The NM_015122.3(FCHO1):​c.28-4G>T variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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)
• Consequence: FCHO1 NM_015122.3 splice_region, intron
• Scores: Splicing: ADA: 0.00001984
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.233

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 (HGNC:):

ACMG classification

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=-0.78).
• BP6: Variant 19-17762758-G-T is Benign according to our data. Variant chr19-17762758-G-T is described in ClinVar as [Likely_benign]. Clinvar id is 2802079.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FCHO1	NM_015122.3	c.28-4G>T		splice_region_variant, intron_variant		ENST00000596536.6	NP_055937.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FCHO1	ENST00000596536.6	c.28-4G>T		splice_region_variant, intron_variant		5	NM_015122.3	ENSP00000470731.1
FCHO1	ENST00000699212.1	c.28-4G>T		splice_region_variant, intron_variant				ENSP00000514208.1
FCHO1	ENST00000594202.6	c.28-4G>T		splice_region_variant, intron_variant		5		ENSP00000473001.1
FCHO1	ENST00000596309.6	c.28-4G>T		splice_region_variant, intron_variant		4		ENSP00000470511.2
FCHO1	ENST00000596951.6	c.28-4G>T		splice_region_variant, intron_variant		5		ENSP00000472417.1
FCHO1	ENST00000600209.6	c.28-4G>T		splice_region_variant, intron_variant		5		ENSP00000469075.2
FCHO1	ENST00000600676.5	c.28-4G>T		splice_region_variant, intron_variant		2		ENSP00000470493.1
FCHO1	ENST00000699176.1	c.28-4G>T		splice_region_variant, intron_variant				ENSP00000514179.1
FCHO1	ENST00000699177.1	c.28-4G>T		splice_region_variant, intron_variant				ENSP00000514180.1
FCHO1	ENST00000699207.1	c.28-4G>T		splice_region_variant, intron_variant				ENSP00000514204.1
FCHO1	ENST00000699209.1	c.28-4G>T		splice_region_variant, intron_variant				ENSP00000514206.1
FCHO1	ENST00000699215.1	c.28-4G>T		splice_region_variant, intron_variant				ENSP00000514211.1
FCHO1	ENST00000699202.1	c.28-4G>T		splice_region_variant, intron_variant				ENSP00000514200.1
FCHO1	ENST00000699214.1	c.28-4G>T		splice_region_variant, intron_variant				ENSP00000514210.1
FCHO1	ENST00000699208.1	c.28-4G>T		splice_region_variant, intron_variant				ENSP00000514205.1
FCHO1	ENST00000699198.1	c.28-4G>T		splice_region_variant, intron_variant				ENSP00000514196.1
FCHO1	ENST00000699199.1	c.28-4G>T		splice_region_variant, intron_variant				ENSP00000514197.1
FCHO1	ENST00000699213.1	c.28-4G>T		splice_region_variant, intron_variant				ENSP00000514209.1
FCHO1	ENST00000699197.1	c.28-4G>T		splice_region_variant, intron_variant				ENSP00000514195.1
FCHO1	ENST00000699200.1	c.28-4G>T		splice_region_variant, intron_variant				ENSP00000514198.1
FCHO1	ENST00000699196.1	c.28-4G>T		splice_region_variant, intron_variant				ENSP00000514194.1
FCHO1	ENST00000699203.1	c.-123-4G>T		splice_region_variant, intron_variant				ENSP00000514201.1
FCHO1	ENST00000699201.1	n.28-4G>T		splice_region_variant, intron_variant				ENSP00000514199.1
FCHO1	ENST00000699205.1	n.28-4G>T		splice_region_variant, intron_variant				ENSP00000514202.1
FCHO1	ENST00000699206.1	n.28-4G>T		splice_region_variant, intron_variant				ENSP00000514203.1
FCHO1	ENST00000699210.1	n.28-4G>T		splice_region_variant, intron_variant				ENSP00000514207.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 31

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Nov 04, 2023

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	4.3
DANN	Benign	0.74
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.000020
dbscSNV1_RF	Benign	0.0
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

No publications associated with this variant yet.

Other links and lift over

hg19: chr19-17873567;