rs117245024

Variant names:

• chr19-17762730-C-A
• rs117245024
• ENST00000597512.1:n.28C>A

Your query was ambiguous. Multiple possible variants found:

• chr19-17762730-C-A
• chr19-17762730-C-T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_015122.3(FCHO1):​c.28-32C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000074 in 1,351,696 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: 31)
  • Exomes 𝑓: 7.4e-7 (0 hom.)
• Consequence: FCHO1 NM_015122.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.140
• 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: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.13494939).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FCHO1	NM_015122.3	c.28-32C>A		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.28-32C>A		intron_variant	Intron 4 of 28	5	NM_015122.3	ENSP00000470731.1
FCHO1	ENST00000699212.1	c.28-32C>A		intron_variant	Intron 4 of 29			ENSP00000514208.1
FCHO1	ENST00000594202.6	c.28-32C>A		intron_variant	Intron 4 of 28	5		ENSP00000473001.1
FCHO1	ENST00000596309.6	c.28-32C>A		intron_variant	Intron 4 of 28	4		ENSP00000470511.2
FCHO1	ENST00000596951.6	c.28-32C>A		intron_variant	Intron 4 of 28	5		ENSP00000472417.1
FCHO1	ENST00000600209.6	c.28-32C>A		intron_variant	Intron 4 of 28	5		ENSP00000469075.2
FCHO1	ENST00000600676.5	c.28-32C>A		intron_variant	Intron 3 of 27	2		ENSP00000470493.1
FCHO1	ENST00000699176.1	c.28-32C>A		intron_variant	Intron 4 of 28			ENSP00000514179.1
FCHO1	ENST00000699177.1	c.28-32C>A		intron_variant	Intron 4 of 28			ENSP00000514180.1
FCHO1	ENST00000699207.1	c.28-32C>A		intron_variant	Intron 4 of 28			ENSP00000514204.1
FCHO1	ENST00000699209.1	c.28-32C>A		intron_variant	Intron 4 of 28			ENSP00000514206.1
FCHO1	ENST00000699215.1	c.28-32C>A		intron_variant	Intron 3 of 27			ENSP00000514211.1
FCHO1	ENST00000699202.1	c.28-32C>A		intron_variant	Intron 4 of 28			ENSP00000514200.1
FCHO1	ENST00000699214.1	c.28-32C>A		intron_variant	Intron 3 of 27			ENSP00000514210.1
FCHO1	ENST00000699208.1	c.28-32C>A		intron_variant	Intron 4 of 27			ENSP00000514205.1
FCHO1	ENST00000699198.1	c.28-32C>A		intron_variant	Intron 4 of 28			ENSP00000514196.1
FCHO1	ENST00000699199.1	c.28-32C>A		intron_variant	Intron 3 of 27			ENSP00000514197.1
FCHO1	ENST00000699213.1	c.28-32C>A		intron_variant	Intron 3 of 27			ENSP00000514209.1
FCHO1	ENST00000699197.1	c.28-32C>A		intron_variant	Intron 4 of 27			ENSP00000514195.1
FCHO1	ENST00000699200.1	c.28-32C>A		intron_variant	Intron 4 of 27			ENSP00000514198.1
FCHO1	ENST00000699196.1	c.28-32C>A		intron_variant	Intron 4 of 26			ENSP00000514194.1
FCHO1	ENST00000699203.1	c.-123-32C>A		intron_variant	Intron 2 of 21			ENSP00000514201.1
FCHO1	ENST00000699201.1	n.28-32C>A		intron_variant	Intron 4 of 27			ENSP00000514199.1
FCHO1	ENST00000699205.1	n.28-32C>A		intron_variant	Intron 4 of 26			ENSP00000514202.1
FCHO1	ENST00000699206.1	n.28-32C>A		intron_variant	Intron 4 of 28			ENSP00000514203.1
FCHO1	ENST00000699210.1	n.28-32C>A		intron_variant	Intron 4 of 27			ENSP00000514207.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 7.40e-7 AC: 1 AN: 1351696 Hom.: 0 Cov.: 22 AF XY: 0.00000147 AC XY: 1 AN XY: 679014

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 31382

American (AMR) AF: 0.00 AC: 0 AN: 44592

Ashkenazi Jewish (ASJ) AF: 0.0000392 AC: 1 AN: 25494

East Asian (EAS) AF: 0.00 AC: 0 AN: 39100

South Asian (SAS) AF: 0.00 AC: 0 AN: 84120

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53372

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5542

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1011362

Other (OTH) AF: 0.00 AC: 0 AN: 56732

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.000000), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Benign	-0.15	T
BayesDel_noAF	Benign	-0.46
CADD	Benign	0.69
DANN	Benign	0.75
FATHMM_MKL	Benign	0.077	N
LIST_S2	Benign	0.33	T
M_CAP	Benign	0.0012	T
MetaRNN	Benign	0.13	T
PhyloP100		-0.14
Sift4G	Benign	1.0	T
Vest4		0.27
MVP		0.41
GERP RS		0.84
PromoterAI		0.0062	Neutral
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

Other links and lift over

dbSNP: rs117245024; hg19: chr19-17873539;