1-52333341-G-A

Variant names:

• chr1-52333341-G-A
• rs2762818
• NM_004799.4:c.3589+423G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_004799.4(ZFYVE9):​c.3589+423G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.772 in 151,540 control chromosomes in the GnomAD database, including 49,463 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 0.77 (49463 hom., cov: 27)
• Consequence: ZFYVE9 NM_004799.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.251
• Publications: 3 publications found

Genes affected

ZFYVE9 (HGNC:6775): (zinc finger FYVE-type containing 9) This gene encodes a double zinc finger motif-containing protein that participates in the transforming growth factor-beta (TGFB) signalling pathway. The encoded protein interacts directly with SMAD2 and SMAD3, and recruits SMAD2 to the TGFB receptor. There are multiple pseudogenes for this gene on chromosomes 2, 15, and X. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Mar 2013]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.926 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZFYVE9	NM_004799.4	c.3589+423G>A		intron_variant	Intron 14 of 18	ENST00000287727.8	NP_004790.2
ZFYVE9	NM_007324.5	c.3412+423G>A		intron_variant	Intron 13 of 17		NP_015563.2
ZFYVE9	XM_011542437.3	c.3589+423G>A		intron_variant	Intron 14 of 18		XP_011540739.1
ZFYVE9	XM_047434674.1	c.3412+423G>A		intron_variant	Intron 13 of 17		XP_047290630.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZFYVE9	ENST00000287727.8	c.3589+423G>A		intron_variant	Intron 14 of 18	5	NM_004799.4	ENSP00000287727.3
ZFYVE9	ENST00000371591.2	c.3589+423G>A		intron_variant	Intron 15 of 19	1		ENSP00000360647.1
ZFYVE9	ENST00000357206.6	c.3412+423G>A		intron_variant	Intron 13 of 17	1		ENSP00000349737.2
ZFYVE9	ENST00000469134.1	n.339+423G>A		intron_variant	Intron 3 of 3	3

Frequencies

GnomAD3 genomes AF: 0.773 AC: 117025 AN: 151424 Hom.: 49450 Cov.: 27

Gnomad AFR AF: 0.394

Gnomad AMI AF: 0.976

Gnomad AMR AF: 0.863

Gnomad ASJ AF: 0.929

Gnomad EAS AF: 0.847

Gnomad SAS AF: 0.830

Gnomad FIN AF: 0.942

Gnomad MID AF: 0.892

Gnomad NFE AF: 0.932

Gnomad OTH AF: 0.823

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

GnomAD4 genome AF: 0.772 AC: 117056 AN: 151540 Hom.: 49463 Cov.: 27 AF XY: 0.776 AC XY: 57450 AN XY: 74050

African (AFR) AF: 0.394 AC: 16199 AN: 41130

American (AMR) AF: 0.863 AC: 13164 AN: 15246

Ashkenazi Jewish (ASJ) AF: 0.929 AC: 3221 AN: 3468

East Asian (EAS) AF: 0.848 AC: 4363 AN: 5146

South Asian (SAS) AF: 0.831 AC: 3981 AN: 4790

European-Finnish (FIN) AF: 0.942 AC: 9879 AN: 10488

Middle Eastern (MID) AF: 0.894 AC: 261 AN: 292

European-Non Finnish (NFE) AF: 0.932 AC: 63370 AN: 67966

Other (OTH) AF: 0.822 AC: 1728 AN: 2102

Alfa AF: 0.853 Hom.: 21411

Bravo AF: 0.751

Asia WGS AF: 0.801 AC: 2788 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.58
DANN	Benign	0.56
PhyloP100		-0.25
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: rs2762818; hg19: chr1-52799013;