4-2388331-A-G

Position:

• chr4-2388331-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+29954T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0696 in 152,280 control chromosomes in the GnomAD database, including 1,134 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 0.070 (1134 hom., cov: 32)
• Consequence: ZFYVE28 NM_020972.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.87

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=-1.0).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.224 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZFYVE28	NM_020972.3	c.39+29954T>C		intron_variant		ENST00000290974.7	NP_066023.2
ZFYVE28	NM_001172656.2	c.39+29954T>C		intron_variant			NP_001166127.1
ZFYVE28	NM_001172657.2	c.39+29954T>C		intron_variant			NP_001166128.1
ZFYVE28	NM_001172658.3	c.39+29954T>C		intron_variant			NP_001166129.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZFYVE28	ENST00000290974.7	c.39+29954T>C		intron_variant		1	NM_020972.3	ENSP00000290974	P2

Frequencies

GnomAD3 genomes AF: 0.0693 AC: 10551 AN: 152162 Hom.: 1126 Cov.: 32

Gnomad AFR AF: 0.227

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0279

Gnomad ASJ AF: 0.0585

Gnomad EAS AF: 0.0597

Gnomad SAS AF: 0.00124

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00949

Gnomad NFE AF: 0.00125

Gnomad OTH AF: 0.0576

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

GnomAD4 genome AF: 0.0696 AC: 10593 AN: 152280 Hom.: 1134 Cov.: 32 AF XY: 0.0675 AC XY: 5029 AN XY: 74458

Gnomad4 AFR AF: 0.227

Gnomad4 AMR AF: 0.0278

Gnomad4 ASJ AF: 0.0585

Gnomad4 EAS AF: 0.0601

Gnomad4 SAS AF: 0.00103

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00125

Gnomad4 OTH AF: 0.0575

Alfa AF: 0.0444 Hom.: 111

Bravo AF: 0.0783

Asia WGS AF: 0.0480 AC: 166 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	0.18
DANN	Benign	0.47
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: rs10488837; hg19: chr4-2390058;