rs3790522

Variant names:

• chr1-52239755-T-C
• rs3790522
• NM_004799.4:c.2178+160T>C

Variant summary

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

The NM_004799.4(ZFYVE9):​c.2178+160T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.228 in 152,158 control chromosomes in the GnomAD database, including 8,192 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 0.23 (8192 hom., cov: 32)
• Consequence: ZFYVE9 NM_004799.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.80
• Publications: 2 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=-0.88).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.598 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZFYVE9	NM_004799.4	c.2178+160T>C		intron_variant	Intron 4 of 18	ENST00000287727.8	NP_004790.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZFYVE9	ENST00000287727.8	c.2178+160T>C		intron_variant	Intron 4 of 18	5	NM_004799.4	ENSP00000287727.3
ZFYVE9	ENST00000371591.2	c.2178+160T>C		intron_variant	Intron 5 of 19	1		ENSP00000360647.1
ZFYVE9	ENST00000357206.6	c.2178+160T>C		intron_variant	Intron 4 of 17	1		ENSP00000349737.2
ZFYVE9	ENST00000361625.5	n.2350+160T>C		intron_variant	Intron 4 of 4	1

Frequencies

GnomAD3 genomes AF: 0.227 AC: 34588 AN: 152040 Hom.: 8152 Cov.: 32

Gnomad AFR AF: 0.604

Gnomad AMI AF: 0.0241

Gnomad AMR AF: 0.137

Gnomad ASJ AF: 0.0711

Gnomad EAS AF: 0.151

Gnomad SAS AF: 0.170

Gnomad FIN AF: 0.0594

Gnomad MID AF: 0.108

Gnomad NFE AF: 0.0685

Gnomad OTH AF: 0.177

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

GnomAD4 genome AF: 0.228 AC: 34673 AN: 152158 Hom.: 8192 Cov.: 32 AF XY: 0.224 AC XY: 16685 AN XY: 74414

African (AFR) AF: 0.604 AC: 25030 AN: 41428

American (AMR) AF: 0.137 AC: 2089 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.0711 AC: 247 AN: 3472

East Asian (EAS) AF: 0.150 AC: 780 AN: 5190

South Asian (SAS) AF: 0.169 AC: 815 AN: 4828

European-Finnish (FIN) AF: 0.0594 AC: 631 AN: 10618

Middle Eastern (MID) AF: 0.106 AC: 31 AN: 292

European-Non Finnish (NFE) AF: 0.0684 AC: 4653 AN: 68010

Other (OTH) AF: 0.178 AC: 375 AN: 2112

Alfa AF: 0.177 Hom.: 1096

Bravo AF: 0.249

Asia WGS AF: 0.197 AC: 686 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	1.8
DANN	Benign	0.27
PhyloP100		-1.8
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: rs3790522; hg19: chr1-52705427;