4-2393570-A-G

Position:

• chr4-2393570-A-G

Variant summary

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

The NM_020972.3(ZFYVE28):​c.39+24715T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.128 in 152,190 control chromosomes in the GnomAD database, including 1,285 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 0.13 (1285 hom., cov: 33)
• Consequence: ZFYVE28 NM_020972.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.87

Genes affected

ZFYVE28 (HGNC:29334): (zinc finger FYVE-type containing 28) Enables phosphatidylinositol-3-phosphate binding activity. Involved in negative regulation of epidermal growth factor-activated receptor activity. Located in cytosol and early endosome membrane. [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=-0.88).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.126 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZFYVE28	NM_020972.3	c.39+24715T>C		intron_variant		ENST00000290974.7	NP_066023.2
ZFYVE28	NM_001172656.2	c.39+24715T>C		intron_variant			NP_001166127.1
ZFYVE28	NM_001172657.2	c.39+24715T>C		intron_variant			NP_001166128.1
ZFYVE28	NM_001172658.3	c.39+24715T>C		intron_variant			NP_001166129.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZFYVE28	ENST00000290974.7	c.39+24715T>C		intron_variant		1	NM_020972.3	ENSP00000290974.3

Frequencies

GnomAD3 genomes AF: 0.128 AC: 19517 AN: 152072 Hom.: 1284 Cov.: 33

Gnomad AFR AF: 0.124

Gnomad AMI AF: 0.0954

Gnomad AMR AF: 0.131

Gnomad ASJ AF: 0.112

Gnomad EAS AF: 0.0731

Gnomad SAS AF: 0.123

Gnomad FIN AF: 0.182

Gnomad MID AF: 0.108

Gnomad NFE AF: 0.128

Gnomad OTH AF: 0.133

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

GnomAD4 genome AF: 0.128 AC: 19527 AN: 152190 Hom.: 1285 Cov.: 33 AF XY: 0.128 AC XY: 9514 AN XY: 74428

Gnomad4 AFR AF: 0.124

Gnomad4 AMR AF: 0.131

Gnomad4 ASJ AF: 0.112

Gnomad4 EAS AF: 0.0733

Gnomad4 SAS AF: 0.123

Gnomad4 FIN AF: 0.182

Gnomad4 NFE AF: 0.128

Gnomad4 OTH AF: 0.134

Alfa AF: 0.0646 Hom.: 92

Bravo AF: 0.123

Asia WGS AF: 0.131 AC: 458 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	0.28
DANN	Benign	0.60
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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: rs959770; hg19: chr4-2395297;