rs10888748

Positions:

• chr1-52162617-A-G

Variant summary

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

The NM_004799.4(ZFYVE9):​c.-143+20214A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.789 in 254,796 control chromosomes in the GnomAD database, including 84,601 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 0.74 (45801 hom., cov: 31)
  • Exomes 𝑓: 0.86 (38800 hom.)
• Consequence: ZFYVE9 NM_004799.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.286

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]

ZFYVE9 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.61).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.889 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZFYVE9	NM_004799.4	c.-143+20214A>G		intron_variant		ENST00000287727.8	NP_004790.2
ZFYVE9	NM_007324.5	c.-143+20214A>G		intron_variant			NP_015563.2
LOC724060		n.52162617A>G		intragenic_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZFYVE9	ENST00000287727.8	c.-143+20214A>G		intron_variant		5	NM_004799.4	ENSP00000287727.3

Frequencies

GnomAD3 genomes AF: 0.738 AC: 112167 AN: 151946 Hom.: 45796 Cov.: 31

Gnomad AFR AF: 0.349

Gnomad AMI AF: 0.947

Gnomad AMR AF: 0.838

Gnomad ASJ AF: 0.899

Gnomad EAS AF: 0.844

Gnomad SAS AF: 0.826

Gnomad FIN AF: 0.928

Gnomad MID AF: 0.867

Gnomad NFE AF: 0.895

Gnomad OTH AF: 0.788

GnomAD4 exome AF: 0.864 AC: 88742 AN: 102732 Hom.: 38800 Cov.: 0 AF XY: 0.866 AC XY: 49524 AN XY: 57172

Gnomad4 AFR exome AF: 0.336

Gnomad4 AMR exome AF: 0.830

Gnomad4 ASJ exome AF: 0.895

Gnomad4 EAS exome AF: 0.834

Gnomad4 SAS exome AF: 0.810

Gnomad4 FIN exome AF: 0.919

Gnomad4 NFE exome AF: 0.891

Gnomad4 OTH exome AF: 0.871

GnomAD4 genome AF: 0.738 AC: 112187 AN: 152064 Hom.: 45801 Cov.: 31 AF XY: 0.743 AC XY: 55257 AN XY: 74332

Gnomad4 AFR AF: 0.348

Gnomad4 AMR AF: 0.838

Gnomad4 ASJ AF: 0.899

Gnomad4 EAS AF: 0.844

Gnomad4 SAS AF: 0.827

Gnomad4 FIN AF: 0.928

Gnomad4 NFE AF: 0.895

Gnomad4 OTH AF: 0.787

Alfa AF: 0.804 Hom.: 16902

Bravo AF: 0.714

Asia WGS AF: 0.793 AC: 2759 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.61
CADD	Benign	2.5
DANN	Benign	0.50

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: rs10888748; hg19: chr1-52628289; COSMIC: COSV55092113; COSMIC: COSV55092113;