rs737452

Variant names:

• chr3-45985918-G-A
• rs737452
• NM_024513.4:c.-112-896C>T

Your query was ambiguous. Multiple possible variants found:

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

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 15 publications found

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 Gene-Disease associations (from GenCC):

• cataract 18

  Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), G2P
• early-onset nuclear cataract

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• total early-onset cataract

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_024513.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FYCO1	NM_024513.4	MANE Select	c.-112-896C>T		intron	N/A	NP_078789.2	Q9BQS8-1
	FYCO1	NM_001386421.1		c.-196-683C>T		intron	N/A	NP_001373350.1	Q9BQS8-1
	FYCO1	NM_001386423.1		c.-112-896C>T		intron	N/A	NP_001373352.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FYCO1	ENST00000296137.7	TSL:1 MANE Select	c.-112-896C>T		intron	N/A	ENSP00000296137.2	Q9BQS8-1
	FYCO1	ENST00000874259.1		c.-196-683C>T		intron	N/A	ENSP00000544318.1
	FYCO1	ENST00000965269.1		c.-112-896C>T		intron	N/A	ENSP00000635328.1

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

African (AFR) AF: 0.106 AC: 4414 AN: 41548

American (AMR) AF: 0.516 AC: 7887 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.388 AC: 1346 AN: 3468

East Asian (EAS) AF: 0.663 AC: 3419 AN: 5158

South Asian (SAS) AF: 0.370 AC: 1787 AN: 4830

European-Finnish (FIN) AF: 0.475 AC: 5017 AN: 10570

Middle Eastern (MID) AF: 0.299 AC: 88 AN: 294

European-Non Finnish (NFE) AF: 0.421 AC: 28634 AN: 67980

Other (OTH) AF: 0.373 AC: 789 AN: 2114

Alfa AF: 0.406 Hom.: 22645

Bravo AF: 0.345

Asia WGS AF: 0.509 AC: 1769 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	1.3
DANN	Benign	0.61
PhyloP100		-0.11
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: rs737452; hg19: chr3-46027410;