4-2393570-A-G

Variant names:

• chr4-2393570-A-G
• rs959770
• NM_020972.3:c.39+24715T>C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 11 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_020972.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZFYVE28	NM_020972.3	MANE Select	c.39+24715T>C		intron	N/A	NP_066023.2	Q9HCC9-1
	ZFYVE28	NM_001172656.2		c.39+24715T>C		intron	N/A	NP_001166127.1	Q9HCC9-2
	ZFYVE28	NM_001172657.2		c.39+24715T>C		intron	N/A	NP_001166128.1	Q9HCC9-6

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZFYVE28	ENST00000290974.7	TSL:1 MANE Select	c.39+24715T>C		intron	N/A	ENSP00000290974.3	Q9HCC9-1
	ZFYVE28	ENST00000503000.1	TSL:1	c.39+24715T>C		intron	N/A	ENSP00000423694.1	Q9HCC9-6
	ZFYVE28	ENST00000511071.5	TSL:5	c.39+24715T>C		intron	N/A	ENSP00000425706.1	Q9HCC9-2

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

African (AFR) AF: 0.124 AC: 5154 AN: 41526

American (AMR) AF: 0.131 AC: 2007 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.112 AC: 389 AN: 3468

East Asian (EAS) AF: 0.0733 AC: 379 AN: 5174

South Asian (SAS) AF: 0.123 AC: 593 AN: 4824

European-Finnish (FIN) AF: 0.182 AC: 1933 AN: 10604

Middle Eastern (MID) AF: 0.109 AC: 32 AN: 294

European-Non Finnish (NFE) AF: 0.128 AC: 8669 AN: 67976

Other (OTH) AF: 0.134 AC: 284 AN: 2116

Alfa AF: 0.120 Hom.: 1951

Bravo AF: 0.123

Asia WGS AF: 0.131 AC: 458 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.28
DANN	Benign	0.60
PhyloP100		-2.9
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
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: rs959770; hg19: chr4-2395297;