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GeneBe

4-2304318-G-A

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_StrongBP6_ModerateBP7BS1BS2

The NM_020972.3(ZFYVE28):c.2022C>T(p.His674=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00116 in 1,597,702 control chromosomes in the GnomAD database, including 37 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0027 ( 8 hom., cov: 35)
Exomes 𝑓: 0.0010 ( 29 hom. )

Consequence

ZFYVE28
NM_020972.3 synonymous

Scores

2

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.920
Variant links:
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -15 ACMG points.

BP4
?
    BP4 - Multiple lines of computational evidence suggest no impact on gene or gene product (conservation, evolutionary, splicing impact, etc.)
Computational evidence support a benign effect (BayesDel_noAF=-0.9).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
Variant 4-2304318-G-A is Benign according to our data. Variant chr4-2304318-G-A is described in ClinVar as [Benign]. Clinvar id is 713067.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
?
    BP7 - A synonymous (silent) variant for which splicing prediction algorithms predict no impact to the splice consensus sequence nor the creation of a new splice site AND the nucleotide is not highly conserved
Synonymous conserved (PhyloP=-0.92 with no splicing effect.
BS1
?
    BS1 - Allele frequency is greater than expected for disorder
Variant frequency is greater than expected in population eas. gnomad4 allele frequency = 0.00267 (407/152358) while in subpopulation EAS AF= 0.0403 (209/5184). AF 95% confidence interval is 0.0358. There are 8 homozygotes in gnomad4. There are 203 alleles in male gnomad4 subpopulation. Median coverage is 35. This position pass quality control queck.
BS2
?
    BS2 - Observed in a healthy adult individual for a recessive (homozygous), dominant (heterozygous), or X-linked (hemizygous) disorder, with full penetrance expected at an early age
High Homozygotes in GnomAd at 8 AR gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
ZFYVE28NM_020972.3 linkuse as main transcriptc.2022C>T p.His674= synonymous_variant 8/13 ENST00000290974.7
ZFYVE28NM_001172656.2 linkuse as main transcriptc.1932C>T p.His644= synonymous_variant 7/12
ZFYVE28NM_001172659.2 linkuse as main transcriptc.1812C>T p.His604= synonymous_variant 8/13

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
ZFYVE28ENST00000290974.7 linkuse as main transcriptc.2022C>T p.His674= synonymous_variant 8/131 NM_020972.3 P2Q9HCC9-1
ENST00000510632.1 linkuse as main transcriptn.263-2573G>A intron_variant, non_coding_transcript_variant 4
ZFYVE28ENST00000511071.5 linkuse as main transcriptc.1932C>T p.His644= synonymous_variant 7/125 A2Q9HCC9-2
ZFYVE28ENST00000515312.5 linkuse as main transcriptc.1812C>T p.His604= synonymous_variant 8/132 A2Q9HCC9-3

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00265
AC:
404
AN:
152240
Hom.:
8
Cov.:
35
show subpopulations
Gnomad AFR
AF:
0.00371
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00170
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.0402
Gnomad SAS
AF:
0.000414
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00316
Gnomad NFE
AF:
0.0000735
Gnomad OTH
AF:
0.00334
GnomAD3 exomes
AF:
0.00367
AC:
866
AN:
235888
Hom.:
21
AF XY:
0.00323
AC XY:
417
AN XY:
129224
show subpopulations
Gnomad AFR exome
AF:
0.00386
Gnomad AMR exome
AF:
0.000151
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.0429
Gnomad SAS exome
AF:
0.000267
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000461
Gnomad OTH exome
AF:
0.00257
GnomAD4 exome
AF:
0.00100
AC:
1445
AN:
1445344
Hom.:
29
Cov.:
30
AF XY:
0.000911
AC XY:
655
AN XY:
719270
show subpopulations
Gnomad4 AFR exome
AF:
0.00389
Gnomad4 AMR exome
AF:
0.000207
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.0243
Gnomad4 SAS exome
AF:
0.000409
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000559
Gnomad4 OTH exome
AF:
0.00406
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00267
AC:
407
AN:
152358
Hom.:
8
Cov.:
35
AF XY:
0.00272
AC XY:
203
AN XY:
74502
show subpopulations
Gnomad4 AFR
AF:
0.00378
Gnomad4 AMR
AF:
0.00170
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.0403
Gnomad4 SAS
AF:
0.000414
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000735
Gnomad4 OTH
AF:
0.00331
Alfa
AF:
0.000276
Hom.:
1
Bravo
AF:
0.00289
Asia WGS
AF:
0.0210
AC:
73
AN:
3478

ClinVar

Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not provided Benign:1
Benign, criteria provided, single submitterclinical testingInvitaeJul 10, 2018- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.90
Cadd
Benign
0.99
Dann
Benign
0.48

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.010
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

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs112076615; hg19: chr4-2306045; API