rs7915

Positions:

• chr15-40814287-A-C
• chr15-40814287-A-G
• chr15-40814287-A-T

Variant summary

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

The NM_001077268.2(ZFYVE19):​c.*61A>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.363 in 1,592,262 control chromosomes in the GnomAD database, including 109,893 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 0.31 (8241 hom., cov: 33)
  • Exomes 𝑓: 0.37 (101652 hom.)
• Consequence: ZFYVE19 NM_001077268.2 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.174

Genes affected

ZFYVE19 (HGNC:20758): (zinc finger FYVE-type containing 19) Enables phosphatidylinositol-3-phosphate binding activity. Involved in abscission; mitotic cytokinesis checkpoint signaling; and negative regulation of cytokinesis. Located in centrosome; cleavage furrow; and midbody. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.634 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ZFYVE19	NM_001077268.2	c.*61A>C		3_prime_UTR_variant	11/11	ENST00000355341.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ZFYVE19	ENST00000355341.8	c.*61A>C		3_prime_UTR_variant	11/11	1	NM_001077268.2	P2

Frequencies

GnomAD3 genomes AF: 0.306 AC: 46598 AN: 152078 Hom.: 8236 Cov.: 33

Gnomad AFR AF: 0.137

Gnomad AMI AF: 0.374

Gnomad AMR AF: 0.330

Gnomad ASJ AF: 0.398

Gnomad EAS AF: 0.652

Gnomad SAS AF: 0.345

Gnomad FIN AF: 0.331

Gnomad MID AF: 0.351

Gnomad NFE AF: 0.364

Gnomad OTH AF: 0.355

GnomAD4 exome AF: 0.369 AC: 532084 AN: 1440066 Hom.: 101652 Cov.: 28 AF XY: 0.370 AC XY: 264909 AN XY: 716476

Gnomad4 AFR exome AF: 0.127

Gnomad4 AMR exome AF: 0.315

Gnomad4 ASJ exome AF: 0.390

Gnomad4 EAS exome AF: 0.675

Gnomad4 SAS exome AF: 0.332

Gnomad4 FIN exome AF: 0.330

Gnomad4 NFE exome AF: 0.373

Gnomad4 OTH exome AF: 0.364

GnomAD4 genome AF: 0.306 AC: 46600 AN: 152196 Hom.: 8241 Cov.: 33 AF XY: 0.309 AC XY: 22986 AN XY: 74396

Gnomad4 AFR AF: 0.137

Gnomad4 AMR AF: 0.330

Gnomad4 ASJ AF: 0.398

Gnomad4 EAS AF: 0.652

Gnomad4 SAS AF: 0.345

Gnomad4 FIN AF: 0.331

Gnomad4 NFE AF: 0.364

Gnomad4 OTH AF: 0.351

Alfa AF: 0.361 Hom.: 20529

Bravo AF: 0.304

Asia WGS AF: 0.441 AC: 1532 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	5.5
DANN	Benign	0.72

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: rs7915; hg19: chr15-41106485;