rs737452

Positions:

• chr3-45985918-G-A
• chr3-45985918-G-C

Variant summary

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

The NM_024513.4(FYCO1):​c.-112-896C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.353 in 152,168 control chromosomes in the GnomAD database, including 11,668 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 0.35 (11668 hom., cov: 33)
• Consequence: FYCO1 NM_024513.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.108

Genes affected

FYCO1 (HGNC:14673): (FYVE and coiled-coil domain autophagy adaptor 1) The gene encodes a Rab7 adapter protein that is implicated in the microtubule transport of autophagosomes. The encoded protein contains a RUN domain, a FYVE-type zinc finger domain, and Golgi dynamics (GOLD) domain. The encoded protein plays a role in microtubule plus end-directed transport of autophagic vesicles through interactions with the small GTPase Rab7, phosphatidylinositol-3-phosphate (PI3P), the autophagosome marker LC3, and the kinesin KIF5. Mutations in this gene are associated with inclusion body myositis (IBM) and autosomal recessive congenital cataracts (CATC2). [provided by RefSeq, Aug 2020]

FYCO1 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.644 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FYCO1	NM_024513.4	c.-112-896C>T		intron_variant		ENST00000296137.7	NP_078789.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FYCO1	ENST00000296137.7	c.-112-896C>T		intron_variant		1	NM_024513.4	ENSP00000296137.2
FYCO1	ENST00000471739.1	n.104-896C>T		intron_variant		4

Frequencies

GnomAD3 genomes AF: 0.353 AC: 53689 AN: 152050 Hom.: 11655 Cov.: 33

Gnomad AFR AF: 0.106

Gnomad AMI AF: 0.366

Gnomad AMR AF: 0.515

Gnomad ASJ AF: 0.388

Gnomad EAS AF: 0.663

Gnomad SAS AF: 0.370

Gnomad FIN AF: 0.475

Gnomad MID AF: 0.301

Gnomad NFE AF: 0.421

Gnomad OTH AF: 0.367

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.353 AC: 53715 AN: 152168 Hom.: 11668 Cov.: 33 AF XY: 0.360 AC XY: 26794 AN XY: 74384

Gnomad4 AFR AF: 0.106

Gnomad4 AMR AF: 0.516

Gnomad4 ASJ AF: 0.388

Gnomad4 EAS AF: 0.663

Gnomad4 SAS AF: 0.370

Gnomad4 FIN AF: 0.475

Gnomad4 NFE AF: 0.421

Gnomad4 OTH AF: 0.373

Alfa AF: 0.414 Hom.: 18458

Bravo AF: 0.345

Asia WGS AF: 0.509 AC: 1769 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	1.3
DANN	Benign	0.61

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: rs737452; hg19: chr3-46027410;