19-17769819-T-G

Variant names:

• chr19-17769819-T-G
• rs4808095
• NM_015122.3:c.337-606T>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_015122.3(FCHO1):​c.337-606T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.449 in 151,944 control chromosomes in the GnomAD database, including 16,168 homozygotes. 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 0.45 (16168 hom., cov: 33)
• Consequence: FCHO1 NM_015122.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0380
• Publications: 9 publications found

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 Gene-Disease associations (from GenCC):

• immunodeficiency 76

  Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: ClinGen, Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.689 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_015122.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FCHO1	NM_015122.3	MANE Select	c.337-606T>G		intron	N/A	NP_055937.1
	FCHO1	NM_001161357.2		c.337-606T>G		intron	N/A	NP_001154829.1
	FCHO1	NM_001161358.2		c.337-606T>G		intron	N/A	NP_001154830.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FCHO1	ENST00000596536.6	TSL:5 MANE Select	c.337-606T>G		intron	N/A	ENSP00000470731.1
	FCHO1	ENST00000699212.1		c.337-606T>G		intron	N/A	ENSP00000514208.1
	FCHO1	ENST00000594202.6	TSL:5	c.337-606T>G		intron	N/A	ENSP00000473001.1

Frequencies

GnomAD3 genomes AF: 0.449 AC: 68167 AN: 151826 Hom.: 16136 Cov.: 33

Gnomad AFR AF: 0.536

Gnomad AMI AF: 0.392

Gnomad AMR AF: 0.535

Gnomad ASJ AF: 0.496

Gnomad EAS AF: 0.709

Gnomad SAS AF: 0.498

Gnomad FIN AF: 0.262

Gnomad MID AF: 0.557

Gnomad NFE AF: 0.379

Gnomad OTH AF: 0.476

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.449 AC: 68248 AN: 151944 Hom.: 16168 Cov.: 33 AF XY: 0.450 AC XY: 33446 AN XY: 74260

African (AFR) AF: 0.537 AC: 22237 AN: 41442

American (AMR) AF: 0.535 AC: 8156 AN: 15238

Ashkenazi Jewish (ASJ) AF: 0.496 AC: 1718 AN: 3464

East Asian (EAS) AF: 0.708 AC: 3648 AN: 5152

South Asian (SAS) AF: 0.499 AC: 2407 AN: 4824

European-Finnish (FIN) AF: 0.262 AC: 2773 AN: 10572

Middle Eastern (MID) AF: 0.568 AC: 167 AN: 294

European-Non Finnish (NFE) AF: 0.379 AC: 25775 AN: 67946

Other (OTH) AF: 0.481 AC: 1012 AN: 2106

Alfa AF: 0.411 Hom.: 43496

Bravo AF: 0.474

Asia WGS AF: 0.606 AC: 2107 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	3.9
DANN	Benign	0.70
PhyloP100		0.038
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs4808095; hg19: chr19-17880628;