7-139109403-A-T

Position:

• chr7-139109403-A-T

Variant summary

Our verdict is Benign. Variant got -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

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

Verdict is Benign. Variant got -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/exons	MANE	Protein	UniProt
ZC3HAV1	NM_020119.4	c.-72T>A		5_prime_UTR_variant	1/13	ENST00000242351.10	NP_064504.2
ZC3HAV1	NM_001363491.2	c.-72T>A		5_prime_UTR_variant	1/13		NP_001350420.1
ZC3HAV1	NM_024625.4	c.-72T>A		5_prime_UTR_variant	1/9		NP_078901.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZC3HAV1	ENST00000242351.10	c.-72T>A		5_prime_UTR_variant	1/13	1	NM_020119.4	ENSP00000242351.5
ZC3HAV1	ENST00000471652.1	c.-72T>A		5_prime_UTR_variant	1/9	1		ENSP00000419855.1
ZC3HAV1	ENST00000680309.1	c.-127-19644T>A		intron_variant				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

Gnomad4 AFR exome AF: 0.240

Gnomad4 AMR exome AF: 0.108

Gnomad4 ASJ exome AF: 0.0766

Gnomad4 EAS exome AF: 0.485

Gnomad4 SAS exome AF: 0.246

Gnomad4 FIN exome AF: 0.173

Gnomad4 NFE exome AF: 0.101

Gnomad4 OTH exome AF: 0.140

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

Gnomad4 AFR AF: 0.240

Gnomad4 AMR AF: 0.118

Gnomad4 ASJ AF: 0.0709

Gnomad4 EAS AF: 0.437

Gnomad4 SAS AF: 0.269

Gnomad4 FIN AF: 0.169

Gnomad4 NFE AF: 0.103

Gnomad4 OTH AF: 0.144

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

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

Other links and lift over

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