NM_020119.4:c.-72T>A

Variant names:

• chr7-139109403-A-T
• rs1814170
• NM_020119.4:c.-72T>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_020119.4(ZC3HAV1):​c.-72T>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.129 in 1,456,454 control chromosomes in the GnomAD database, including 16,627 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 0.16 (2510 hom., cov: 32)
  • Exomes 𝑓: 0.12 (14117 hom.)
• Consequence: ZC3HAV1 NM_020119.4 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.03
• Publications: 12 publications found

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]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.7).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.422 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZC3HAV1	NM_020119.4	c.-72T>A		5_prime_UTR_variant	Exon 1 of 13	ENST00000242351.10	NP_064504.2
ZC3HAV1	NM_001363491.2	c.-72T>A		5_prime_UTR_variant	Exon 1 of 13		NP_001350420.1
ZC3HAV1	NM_024625.4	c.-72T>A		5_prime_UTR_variant	Exon 1 of 9		NP_078901.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZC3HAV1	ENST00000242351.10	c.-72T>A		5_prime_UTR_variant	Exon 1 of 13	1	NM_020119.4	ENSP00000242351.5
ZC3HAV1	ENST00000471652.1	c.-72T>A		5_prime_UTR_variant	Exon 1 of 9	1		ENSP00000419855.1
ZC3HAV1	ENST00000680309.1	c.-127-19644T>A		intron_variant	Intron 1 of 12			ENSP00000505045.1
ZC3HAV1	ENST00000464606.5	c.-72T>A		upstream_gene_variant		5		ENSP00000418385.1

Frequencies

GnomAD3 genomes AF: 0.163 AC: 24775 AN: 151970 Hom.: 2511 Cov.: 32

Gnomad AFR AF: 0.240

Gnomad AMI AF: 0.139

Gnomad AMR AF: 0.118

Gnomad ASJ AF: 0.0709

Gnomad EAS AF: 0.437

Gnomad SAS AF: 0.269

Gnomad FIN AF: 0.169

Gnomad MID AF: 0.0955

Gnomad NFE AF: 0.103

Gnomad OTH AF: 0.145

GnomAD4 exome AF: 0.125 AC: 162872 AN: 1304366 Hom.: 14117 Cov.: 30 AF XY: 0.128 AC XY: 80996 AN XY: 634668

African (AFR) AF: 0.240 AC: 7027 AN: 29320

American (AMR) AF: 0.108 AC: 2702 AN: 25074

Ashkenazi Jewish (ASJ) AF: 0.0766 AC: 1523 AN: 19870

East Asian (EAS) AF: 0.485 AC: 17026 AN: 35110

South Asian (SAS) AF: 0.246 AC: 16368 AN: 66480

European-Finnish (FIN) AF: 0.173 AC: 5736 AN: 33062

Middle Eastern (MID) AF: 0.105 AC: 387 AN: 3676

European-Non Finnish (NFE) AF: 0.101 AC: 104528 AN: 1037526

Other (OTH) AF: 0.140 AC: 7575 AN: 54248

GnomAD4 genome AF: 0.163 AC: 24807 AN: 152088 Hom.: 2510 Cov.: 32 AF XY: 0.168 AC XY: 12521 AN XY: 74360

African (AFR) AF: 0.240 AC: 9980 AN: 41500

American (AMR) AF: 0.118 AC: 1807 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.0709 AC: 246 AN: 3470

East Asian (EAS) AF: 0.437 AC: 2249 AN: 5150

South Asian (SAS) AF: 0.269 AC: 1297 AN: 4826

European-Finnish (FIN) AF: 0.169 AC: 1791 AN: 10594

Middle Eastern (MID) AF: 0.106 AC: 31 AN: 292

European-Non Finnish (NFE) AF: 0.103 AC: 6976 AN: 67944

Other (OTH) AF: 0.144 AC: 304 AN: 2110

Alfa AF: 0.0417 Hom.: 34

Bravo AF: 0.159

Asia WGS AF: 0.334 AC: 1158 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.70
CADD	Benign	9.2
DANN	Benign	0.89
PhyloP100		-2.0
PromoterAI		0.091	Neutral
Mutation Taster		=300/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs1814170; hg19: chr7-138794149; COSMIC: COSV54301289; COSMIC: COSV54301289;