chr19-17755203-T-G

Variant names:

• chr19-17755203-T-G
• rs762048955
• NM_015122.3:c.27+12T>G

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 2P and 6B. PM2 BP4_Strong BP6_Moderate

The NM_015122.3(FCHO1):​c.27+12T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000511 in 1,603,516 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.000020 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000054 (0 hom.)
• Consequence: FCHO1 NM_015122.3 intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.210
• 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 -4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BP6: Variant 19-17755203-T-G is Benign according to our data. Variant chr19-17755203-T-G is described in ClinVar as [Likely_benign]. Clinvar id is 1540460.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	c.27+12T>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+12T>G		intron_variant	Intron 4 of 28	5	NM_015122.3	ENSP00000470731.1
FCHO1	ENST00000699212.1	c.27+12T>G		intron_variant	Intron 4 of 29			ENSP00000514208.1
FCHO1	ENST00000594202.6	c.27+12T>G		intron_variant	Intron 4 of 28	5		ENSP00000473001.1
FCHO1	ENST00000596309.6	c.27+12T>G		intron_variant	Intron 4 of 28	4		ENSP00000470511.2
FCHO1	ENST00000596951.6	c.27+12T>G		intron_variant	Intron 4 of 28	5		ENSP00000472417.1
FCHO1	ENST00000600209.6	c.27+12T>G		intron_variant	Intron 4 of 28	5		ENSP00000469075.2
FCHO1	ENST00000600676.5	c.27+12T>G		intron_variant	Intron 3 of 27	2		ENSP00000470493.1
FCHO1	ENST00000699176.1	c.27+12T>G		intron_variant	Intron 4 of 28			ENSP00000514179.1
FCHO1	ENST00000699177.1	c.27+12T>G		intron_variant	Intron 4 of 28			ENSP00000514180.1
FCHO1	ENST00000699207.1	c.27+12T>G		intron_variant	Intron 4 of 28			ENSP00000514204.1
FCHO1	ENST00000699209.1	c.27+12T>G		intron_variant	Intron 4 of 28			ENSP00000514206.1
FCHO1	ENST00000699215.1	c.27+12T>G		intron_variant	Intron 3 of 27			ENSP00000514211.1
FCHO1	ENST00000699202.1	c.27+12T>G		intron_variant	Intron 4 of 28			ENSP00000514200.1
FCHO1	ENST00000699214.1	c.27+12T>G		intron_variant	Intron 3 of 27			ENSP00000514210.1
FCHO1	ENST00000699208.1	c.27+12T>G		intron_variant	Intron 4 of 27			ENSP00000514205.1
FCHO1	ENST00000699198.1	c.27+12T>G		intron_variant	Intron 4 of 28			ENSP00000514196.1
FCHO1	ENST00000699199.1	c.27+12T>G		intron_variant	Intron 3 of 27			ENSP00000514197.1
FCHO1	ENST00000699213.1	c.27+12T>G		intron_variant	Intron 3 of 27			ENSP00000514209.1
FCHO1	ENST00000699197.1	c.27+12T>G		intron_variant	Intron 4 of 27			ENSP00000514195.1
FCHO1	ENST00000699200.1	c.27+12T>G		intron_variant	Intron 4 of 27			ENSP00000514198.1
FCHO1	ENST00000699196.1	c.27+12T>G		intron_variant	Intron 4 of 26			ENSP00000514194.1
FCHO1	ENST00000699203.1	c.-124+737T>G		intron_variant	Intron 2 of 21			ENSP00000514201.1
FCHO1	ENST00000699201.1	n.27+12T>G		intron_variant	Intron 4 of 27			ENSP00000514199.1
FCHO1	ENST00000699205.1	n.27+12T>G		intron_variant	Intron 4 of 26			ENSP00000514202.1
FCHO1	ENST00000699206.1	n.27+12T>G		intron_variant	Intron 4 of 28			ENSP00000514203.1
FCHO1	ENST00000699210.1	n.27+12T>G		intron_variant	Intron 4 of 27			ENSP00000514207.1

Frequencies

GnomAD3 genomes AF: 0.0000197 AC: 3 AN: 152034 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000242

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000294

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000165 AC: 4 AN: 242128 AF XY: 0.0000305

Gnomad AFR exome AF: 0.0000625

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000182

Gnomad OTH exome AF: 0.000170

GnomAD4 exome AF: 0.0000544 AC: 79 AN: 1451482 Hom.: 0 Cov.: 29 AF XY: 0.0000527 AC XY: 38 AN XY: 721398

African (AFR) AF: 0.00 AC: 0 AN: 33066

American (AMR) AF: 0.00 AC: 0 AN: 43026

Ashkenazi Jewish (ASJ) AF: 0.0000391 AC: 1 AN: 25558

East Asian (EAS) AF: 0.00 AC: 0 AN: 39314

South Asian (SAS) AF: 0.00 AC: 0 AN: 85326

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53218

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5708

European-Non Finnish (NFE) AF: 0.0000669 AC: 74 AN: 1106284

Other (OTH) AF: 0.0000667 AC: 4 AN: 59982

GnomAD4 genome AF: 0.0000197 AC: 3 AN: 152034 Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1 AN XY: 74254

African (AFR) AF: 0.0000242 AC: 1 AN: 41388

American (AMR) AF: 0.00 AC: 0 AN: 15254

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5178

South Asian (SAS) AF: 0.00 AC: 0 AN: 4814

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10602

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.0000294 AC: 2 AN: 68008

Other (OTH) AF: 0.00 AC: 0 AN: 2092

Alfa AF: 0.0000712 Hom.: 0

Bravo AF: 0.0000151

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Jul 15, 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	-0.83
CADD	Benign	5.9
DANN	Benign	0.70
PhyloP100		0.21
PromoterAI		0.018	Neutral

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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: rs762048955; hg19: chr19-17866012;