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GeneBe

7-139055274-C-T

Variant summary

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

The NM_020119.4(ZC3HAV1):c.2118G>A(p.Ser706=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000896 in 1,613,132 control chromosomes in the GnomAD database, including 6 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0048 ( 2 hom., cov: 33)
Exomes 𝑓: 0.00049 ( 4 hom. )

Consequence

ZC3HAV1
NM_020119.4 synonymous

Scores

2

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -2.04
Variant links:
Genes affected
ZC3HAV1 (HGNC:23721): (zinc finger CCCH-type containing, antiviral 1) This gene encodes a CCCH-type zinc finger protein. This antiviral protein inhibits viral replication by recruiting cellular RNA degradation machineries to degrade viral mRNAs. The encoded protein plays an important role in the innate immune response against multiple DNA and RNA viruses, including Ebola virus, HIV and SARS-CoV-2 (which causes COVID-19). [provided by RefSeq, Sep 2021]

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=-0.73).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
Variant 7-139055274-C-T is Benign according to our data. Variant chr7-139055274-C-T is described in ClinVar as [Benign]. Clinvar id is 775256.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=-2.04 with no splicing effect.
BS1
?
    BS1 - Allele frequency is greater than expected for disorder
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0048 (731/152324) while in subpopulation AFR AF= 0.0165 (688/41582). AF 95% confidence interval is 0.0155. There are 2 homozygotes in gnomad4. There are 356 alleles in male gnomad4 subpopulation. Median coverage is 33. 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 2 AR gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
ZC3HAV1NM_020119.4 linkuse as main transcriptc.2118G>A p.Ser706= synonymous_variant 10/13 ENST00000242351.10
ZC3HAV1NM_001363491.2 linkuse as main transcriptc.2484G>A p.Ser828= synonymous_variant 10/13

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
ZC3HAV1ENST00000242351.10 linkuse as main transcriptc.2118G>A p.Ser706= synonymous_variant 10/131 NM_020119.4 A2Q7Z2W4-1
ZC3HAV1ENST00000464606.5 linkuse as main transcriptc.2484G>A p.Ser828= synonymous_variant 10/135 P2
ZC3HAV1ENST00000680309.1 linkuse as main transcriptc.1683G>A p.Ser561= synonymous_variant 10/13

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00479
AC:
729
AN:
152206
Hom.:
2
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.0165
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00183
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.000207
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00316
Gnomad NFE
AF:
0.0000588
Gnomad OTH
AF:
0.00431
GnomAD3 exomes
AF:
0.00140
AC:
351
AN:
250798
Hom.:
2
AF XY:
0.00103
AC XY:
140
AN XY:
135534
show subpopulations
Gnomad AFR exome
AF:
0.0191
Gnomad AMR exome
AF:
0.000878
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.0000329
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000264
Gnomad OTH exome
AF:
0.000984
GnomAD4 exome
AF:
0.000489
AC:
714
AN:
1460808
Hom.:
4
Cov.:
30
AF XY:
0.000425
AC XY:
309
AN XY:
726620
show subpopulations
Gnomad4 AFR exome
AF:
0.0174
Gnomad4 AMR exome
AF:
0.000941
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000465
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000153
Gnomad4 OTH exome
AF:
0.00109
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00480
AC:
731
AN:
152324
Hom.:
2
Cov.:
33
AF XY:
0.00478
AC XY:
356
AN XY:
74494
show subpopulations
Gnomad4 AFR
AF:
0.0165
Gnomad4 AMR
AF:
0.00183
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.000207
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000588
Gnomad4 OTH
AF:
0.00426
Alfa
AF:
0.00217
Hom.:
3
Bravo
AF:
0.00562
Asia WGS
AF:
0.000866
AC:
3
AN:
3478
EpiCase
AF:
0.000109
EpiControl
AF:
0.0000593

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 testingInvitaeJun 29, 2018- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.73
Cadd
Benign
0.97
Dann
Benign
0.40
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.1

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: rs114114457; hg19: chr7-138740020; API