rs1200485

Variant names:

• chr5-73089231-A-G
• rs1200485
• NM_138782.3:c.*1141A>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 10 publications found

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

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
FCHO2	NM_138782.3	c.*1141A>G		3_prime_UTR_variant	Exon 26 of 26	ENST00000430046.7	NP_620137.2
FCHO2	NM_001146032.2	c.*1141A>G		3_prime_UTR_variant	Exon 25 of 25		NP_001139504.1
FCHO2	XM_017009016.3	c.*1141A>G		3_prime_UTR_variant	Exon 25 of 25		XP_016864505.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FCHO2	ENST00000430046.7	c.*1141A>G		3_prime_UTR_variant	Exon 26 of 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

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AF: 0.517 AC: 218 AN: 422

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 1.00 AC: 2 AN: 2

Other (OTH) AF: 0.250 AC: 1 AN: 4

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

African (AFR) AF: 0.281 AC: 11646 AN: 41486

American (AMR) AF: 0.610 AC: 9309 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.542 AC: 1880 AN: 3466

East Asian (EAS) AF: 0.367 AC: 1901 AN: 5180

South Asian (SAS) AF: 0.516 AC: 2489 AN: 4820

European-Finnish (FIN) AF: 0.583 AC: 6159 AN: 10556

Middle Eastern (MID) AF: 0.588 AC: 173 AN: 294

European-Non Finnish (NFE) AF: 0.540 AC: 36680 AN: 67884

Other (OTH) AF: 0.500 AC: 1057 AN: 2112

Alfa AF: 0.503 Hom.: 11383

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
PhyloP100		0.42
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: rs1200485; hg19: chr5-72385058; COSMIC: COSV59278311; COSMIC: COSV59278311;