14-73014626-T-C

Position:

• chr14-73014626-T-C

Variant summary

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

The NM_021260.4(ZFYVE1):​c.483+9400A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.468 in 152,110 control chromosomes in the GnomAD database, including 17,078 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 (17078 hom., cov: 32)
• Consequence: ZFYVE1 NM_021260.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.242

Genes affected

ZFYVE1 (HGNC:13180): (zinc finger FYVE-type containing 1) The FYVE domain mediates the recruitment of proteins involved in membrane trafficking and cell signaling to phosphatidylinositol 3-phosphate-containing membranes. This protein contains two zinc-binding FYVE domains in tandem and is reported to localize to the Golgi apparatus. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Aug 2013]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.517 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZFYVE1	NM_021260.4	c.483+9400A>G		intron_variant		ENST00000556143.6	NP_067083.1
ZFYVE1	NM_001281734.2	c.483+9400A>G		intron_variant			NP_001268663.1
ZFYVE1	XM_047431481.1	c.483+9400A>G		intron_variant			XP_047287437.1
ZFYVE1	XM_047431482.1	c.-770-1679A>G		intron_variant			XP_047287438.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZFYVE1	ENST00000556143.6	c.483+9400A>G		intron_variant		1	NM_021260.4	ENSP00000450742.1
ZFYVE1	ENST00000318876.9	c.483+9400A>G		intron_variant		1		ENSP00000326921.5
ZFYVE1	ENST00000553891.5	c.483+9400A>G		intron_variant		5		ENSP00000452442.1

Frequencies

GnomAD3 genomes AF: 0.468 AC: 71118 AN: 151992 Hom.: 17053 Cov.: 32

Gnomad AFR AF: 0.507

Gnomad AMI AF: 0.359

Gnomad AMR AF: 0.418

Gnomad ASJ AF: 0.464

Gnomad EAS AF: 0.382

Gnomad SAS AF: 0.535

Gnomad FIN AF: 0.346

Gnomad MID AF: 0.554

Gnomad NFE AF: 0.477

Gnomad OTH AF: 0.465

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

GnomAD4 genome AF: 0.468 AC: 71198 AN: 152110 Hom.: 17078 Cov.: 32 AF XY: 0.461 AC XY: 34284 AN XY: 74360

Gnomad4 AFR AF: 0.508

Gnomad4 AMR AF: 0.419

Gnomad4 ASJ AF: 0.464

Gnomad4 EAS AF: 0.382

Gnomad4 SAS AF: 0.534

Gnomad4 FIN AF: 0.346

Gnomad4 NFE AF: 0.477

Gnomad4 OTH AF: 0.468

Alfa AF: 0.465 Hom.: 15635

Bravo AF: 0.473

Asia WGS AF: 0.476 AC: 1656 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	5.3
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: rs7155380; hg19: chr14-73481334;