rs3790522

chr1-52239755-T-C

Variant summary

Our verdict is Benign. Variant got -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

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

Verdict is Benign. Variant got -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/exons	MANE	UniProt
ZFYVE9	NM_004799.4	c.2178+160T>C		intron_variant		ENST00000287727.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ZFYVE9	ENST00000287727.8	c.2178+160T>C		intron_variant		5	NM_004799.4	P1
ZFYVE9	ENST00000357206.6	c.2178+160T>C		intron_variant		1
ZFYVE9	ENST00000371591.2	c.2178+160T>C		intron_variant		1		P1
ZFYVE9	ENST00000361625.5	n.2350+160T>C		intron_variant, non_coding_transcript_variant		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

Gnomad4 AFR AF: 0.604

Gnomad4 AMR AF: 0.137

Gnomad4 ASJ AF: 0.0711

Gnomad4 EAS AF: 0.150

Gnomad4 SAS AF: 0.169

Gnomad4 FIN AF: 0.0594

Gnomad4 NFE AF: 0.0684

Gnomad4 OTH AF: 0.178

Alfa AF: 0.166 Hom.: 960

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

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: rs3790522; hg19: chr1-52705427;