19-17755200-C-G

Variant names:

• chr19-17755200-C-G
• rs544351378
• NM_015122.3:c.27+9C>G

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_015122.3(FCHO1):​c.27+9C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000275 in 1,453,730 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: not found (cov: 32)
  • Exomes 𝑓: 0.0000028 (0 hom.)
• Consequence: FCHO1 NM_015122.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.62
• Publications: 0 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FCHO1	NM_015122.3	c.27+9C>G		intron_variant	Intron 4 of 28	ENST00000596536.6	NP_055937.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FCHO1	ENST00000596536.6	c.27+9C>G		intron_variant	Intron 4 of 28	5	NM_015122.3	ENSP00000470731.1
FCHO1	ENST00000699212.1	c.27+9C>G		intron_variant	Intron 4 of 29			ENSP00000514208.1
FCHO1	ENST00000594202.6	c.27+9C>G		intron_variant	Intron 4 of 28	5		ENSP00000473001.1
FCHO1	ENST00000596309.6	c.27+9C>G		intron_variant	Intron 4 of 28	4		ENSP00000470511.2
FCHO1	ENST00000596951.6	c.27+9C>G		intron_variant	Intron 4 of 28	5		ENSP00000472417.1
FCHO1	ENST00000600209.6	c.27+9C>G		intron_variant	Intron 4 of 28	5		ENSP00000469075.2
FCHO1	ENST00000600676.5	c.27+9C>G		intron_variant	Intron 3 of 27	2		ENSP00000470493.1
FCHO1	ENST00000699176.1	c.27+9C>G		intron_variant	Intron 4 of 28			ENSP00000514179.1
FCHO1	ENST00000699177.1	c.27+9C>G		intron_variant	Intron 4 of 28			ENSP00000514180.1
FCHO1	ENST00000699207.1	c.27+9C>G		intron_variant	Intron 4 of 28			ENSP00000514204.1
FCHO1	ENST00000699209.1	c.27+9C>G		intron_variant	Intron 4 of 28			ENSP00000514206.1
FCHO1	ENST00000699215.1	c.27+9C>G		intron_variant	Intron 3 of 27			ENSP00000514211.1
FCHO1	ENST00000699202.1	c.27+9C>G		intron_variant	Intron 4 of 28			ENSP00000514200.1
FCHO1	ENST00000699214.1	c.27+9C>G		intron_variant	Intron 3 of 27			ENSP00000514210.1
FCHO1	ENST00000699208.1	c.27+9C>G		intron_variant	Intron 4 of 27			ENSP00000514205.1
FCHO1	ENST00000699198.1	c.27+9C>G		intron_variant	Intron 4 of 28			ENSP00000514196.1
FCHO1	ENST00000699199.1	c.27+9C>G		intron_variant	Intron 3 of 27			ENSP00000514197.1
FCHO1	ENST00000699213.1	c.27+9C>G		intron_variant	Intron 3 of 27			ENSP00000514209.1
FCHO1	ENST00000699197.1	c.27+9C>G		intron_variant	Intron 4 of 27			ENSP00000514195.1
FCHO1	ENST00000699200.1	c.27+9C>G		intron_variant	Intron 4 of 27			ENSP00000514198.1
FCHO1	ENST00000699196.1	c.27+9C>G		intron_variant	Intron 4 of 26			ENSP00000514194.1
FCHO1	ENST00000699203.1	c.-124+734C>G		intron_variant	Intron 2 of 21			ENSP00000514201.1
FCHO1	ENST00000699201.1	n.27+9C>G		intron_variant	Intron 4 of 27			ENSP00000514199.1
FCHO1	ENST00000699205.1	n.27+9C>G		intron_variant	Intron 4 of 26			ENSP00000514202.1
FCHO1	ENST00000699206.1	n.27+9C>G		intron_variant	Intron 4 of 28			ENSP00000514203.1
FCHO1	ENST00000699210.1	n.27+9C>G		intron_variant	Intron 4 of 27			ENSP00000514207.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000275 AC: 4 AN: 1453730 Hom.: 0 Cov.: 30 AF XY: 0.00000277 AC XY: 2 AN XY: 722802

African (AFR) AF: 0.00 AC: 0 AN: 33122

American (AMR) AF: 0.00 AC: 0 AN: 43334

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25642

East Asian (EAS) AF: 0.00 AC: 0 AN: 39374

South Asian (SAS) AF: 0.00 AC: 0 AN: 85496

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53256

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5720

European-Non Finnish (NFE) AF: 0.00000361 AC: 4 AN: 1107740

Other (OTH) AF: 0.00 AC: 0 AN: 60046

GnomAD4 genome Cov.: 32

Alfa AF: 0.0000284 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.018
DANN	Benign	0.60
PhyloP100		-1.6
PromoterAI		-0.023	Neutral

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.060		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: rs544351378; hg19: chr19-17866009;