rs12644662

Variant names:

• chr4-2403611-C-A
• rs12644662
• NM_020972.3:c.39+14674G>T

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+14674G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.168 in 152,016 control chromosomes in the GnomAD database, including 2,616 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 0.17 (2616 hom., cov: 32)
• Consequence: ZFYVE28 NM_020972.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.116
• Publications: 3 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=-0.9).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.219 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+14674G>T		intron	N/A	NP_066023.2	Q9HCC9-1
	ZFYVE28	NM_001172656.2		c.39+14674G>T		intron	N/A	NP_001166127.1	Q9HCC9-2
	ZFYVE28	NM_001172657.2		c.39+14674G>T		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+14674G>T		intron	N/A	ENSP00000290974.3	Q9HCC9-1
	ZFYVE28	ENST00000503000.1	TSL:1	c.39+14674G>T		intron	N/A	ENSP00000423694.1	Q9HCC9-6
	ZFYVE28	ENST00000511071.5	TSL:5	c.39+14674G>T		intron	N/A	ENSP00000425706.1	Q9HCC9-2

Frequencies

GnomAD3 genomes AF: 0.168 AC: 25557 AN: 151898 Hom.: 2614 Cov.: 32

Gnomad AFR AF: 0.0696

Gnomad AMI AF: 0.285

Gnomad AMR AF: 0.190

Gnomad ASJ AF: 0.276

Gnomad EAS AF: 0.163

Gnomad SAS AF: 0.205

Gnomad FIN AF: 0.108

Gnomad MID AF: 0.303

Gnomad NFE AF: 0.222

Gnomad OTH AF: 0.203

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

GnomAD4 genome AF: 0.168 AC: 25559 AN: 152016 Hom.: 2616 Cov.: 32 AF XY: 0.165 AC XY: 12239 AN XY: 74298

African (AFR) AF: 0.0695 AC: 2886 AN: 41516

American (AMR) AF: 0.191 AC: 2916 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.276 AC: 958 AN: 3466

East Asian (EAS) AF: 0.163 AC: 837 AN: 5148

South Asian (SAS) AF: 0.206 AC: 993 AN: 4812

European-Finnish (FIN) AF: 0.108 AC: 1142 AN: 10576

Middle Eastern (MID) AF: 0.305 AC: 89 AN: 292

European-Non Finnish (NFE) AF: 0.222 AC: 15061 AN: 67920

Other (OTH) AF: 0.200 AC: 419 AN: 2100

Alfa AF: 0.185 Hom.: 363

Bravo AF: 0.173

Asia WGS AF: 0.175 AC: 610 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	2.5
DANN	Benign	0.71
PhyloP100		0.12
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: rs12644662; hg19: chr4-2405338;