rs4602560

Variant names:

• chr4-2291194-A-G
• rs4602560
• NM_020972.3:c.2051+13095T>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.2051+13095T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.698 in 152,042 control chromosomes in the GnomAD database, including 38,285 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 0.70 (38285 hom., cov: 32)
• Consequence: ZFYVE28 NM_020972.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.00
• Publications: 7 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=-1.0).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.866 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZFYVE28	NM_020972.3	c.2051+13095T>C		intron_variant	Intron 8 of 12	ENST00000290974.7	NP_066023.2
ZFYVE28	NM_001172656.2	c.1961+13095T>C		intron_variant	Intron 7 of 11		NP_001166127.1
ZFYVE28	NM_001172659.2	c.1841+13095T>C		intron_variant	Intron 8 of 12		NP_001166130.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZFYVE28	ENST00000290974.7	c.2051+13095T>C		intron_variant	Intron 8 of 12	1	NM_020972.3	ENSP00000290974.3
ZFYVE28	ENST00000511071.5	c.1961+13095T>C		intron_variant	Intron 7 of 11	5		ENSP00000425706.1
ZFYVE28	ENST00000515312.5	c.1841+13095T>C		intron_variant	Intron 8 of 12	2		ENSP00000426299.1

Frequencies

GnomAD3 genomes AF: 0.698 AC: 106055 AN: 151924 Hom.: 38238 Cov.: 32

Gnomad AFR AF: 0.873

Gnomad AMI AF: 0.781

Gnomad AMR AF: 0.708

Gnomad ASJ AF: 0.661

Gnomad EAS AF: 0.328

Gnomad SAS AF: 0.621

Gnomad FIN AF: 0.671

Gnomad MID AF: 0.653

Gnomad NFE AF: 0.629

Gnomad OTH AF: 0.682

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

GnomAD4 genome AF: 0.698 AC: 106158 AN: 152042 Hom.: 38285 Cov.: 32 AF XY: 0.699 AC XY: 51969 AN XY: 74298

African (AFR) AF: 0.874 AC: 36247 AN: 41496

American (AMR) AF: 0.708 AC: 10826 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.661 AC: 2293 AN: 3468

East Asian (EAS) AF: 0.328 AC: 1692 AN: 5156

South Asian (SAS) AF: 0.621 AC: 2982 AN: 4802

European-Finnish (FIN) AF: 0.671 AC: 7081 AN: 10558

Middle Eastern (MID) AF: 0.637 AC: 186 AN: 292

European-Non Finnish (NFE) AF: 0.628 AC: 42710 AN: 67956

Other (OTH) AF: 0.675 AC: 1429 AN: 2116

Alfa AF: 0.655 Hom.: 9790

Bravo AF: 0.705

Asia WGS AF: 0.505 AC: 1759 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.46
DANN	Benign	0.10
PhyloP100		-2.0
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: rs4602560; hg19: chr4-2292921;