rs1200485

Positions:

• chr5-73089231-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_138782.3(FCHO2):​c.*1141A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.473 in 152,402 control chromosomes in the GnomAD database, including 18,175 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 0.47 (18122 hom., cov: 32)
  • Exomes 𝑓: 0.52 (53 hom.)
• Consequence: FCHO2 NM_138782.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.422

Genes affected

FCHO2 (HGNC:25180): (FCH and mu domain containing endocytic adaptor 2) Enables identical protein binding activity. Involved in clathrin coat assembly and clathrin-dependent endocytosis. Located in clathrin-coated pit and clathrin-coated vesicle. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.6 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FCHO2	NM_138782.3	c.*1141A>G		3_prime_UTR_variant	26/26	ENST00000430046.7	NP_620137.2
FCHO2	NM_001146032.2	c.*1141A>G		3_prime_UTR_variant	25/25		NP_001139504.1
FCHO2	XM_017009016.3	c.*1141A>G		3_prime_UTR_variant	25/25		XP_016864505.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FCHO2	ENST00000430046.7	c.*1141A>G		3_prime_UTR_variant	26/26	1	NM_138782.3	ENSP00000393776.2

Frequencies

GnomAD3 genomes AF: 0.473 AC: 71785 AN: 151856 Hom.: 18114 Cov.: 32

Gnomad AFR AF: 0.281

Gnomad AMI AF: 0.576

Gnomad AMR AF: 0.610

Gnomad ASJ AF: 0.542

Gnomad EAS AF: 0.367

Gnomad SAS AF: 0.516

Gnomad FIN AF: 0.583

Gnomad MID AF: 0.570

Gnomad NFE AF: 0.540

Gnomad OTH AF: 0.502

GnomAD4 exome AF: 0.516 AC: 221 AN: 428 Hom.: 53 Cov.: 0 AF XY: 0.550 AC XY: 142 AN XY: 258

Gnomad4 FIN exome AF: 0.517

Gnomad4 NFE exome AF: 1.00

Gnomad4 OTH exome AF: 0.250

GnomAD4 genome AF: 0.473 AC: 71819 AN: 151974 Hom.: 18122 Cov.: 32 AF XY: 0.476 AC XY: 35348 AN XY: 74276

Gnomad4 AFR AF: 0.281

Gnomad4 AMR AF: 0.610

Gnomad4 ASJ AF: 0.542

Gnomad4 EAS AF: 0.367

Gnomad4 SAS AF: 0.516

Gnomad4 FIN AF: 0.583

Gnomad4 NFE AF: 0.540

Gnomad4 OTH AF: 0.500

Alfa AF: 0.519 Hom.: 7983

Bravo AF: 0.467

Asia WGS AF: 0.457 AC: 1582 AN: 3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	1.0
DANN	Benign	0.70

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

Publications

LitVar

Other links and lift over

dbSNP: rs1200485; hg19: chr5-72385058; COSMIC: COSV59278311; COSMIC: COSV59278311;