rs2073145

Variant names:

• chr20-57615578-C-A
• rs2073145
• NM_030776.3:c.262G>T

Your query was ambiguous. Multiple possible variants found:

• chr20-57615578-C-A
• chr20-57615578-C-G
• chr20-57615578-C-T

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_030776.3(ZBP1):​c.262G>T​(p.Glu88*) variant causes a stop gained, splice region change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as (no stars). Variant results in nonsense mediated mRNA decay.

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: ZBP1 NM_030776.3 stop_gained, splice_region
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.387
• Publications: 0 publications found

Genes affected

ZBP1 (HGNC:16176): (Z-DNA binding protein 1) This gene encodes a Z-DNA binding protein. The encoded protein plays a role in the innate immune response by binding to foreign DNA and inducing type-I interferon production. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene. [provided by RefSeq, Dec 2011]

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_030776.3. 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
	ZBP1	NM_030776.3	MANE Select	c.262G>T	p.Glu88*	stop_gained splice_region	Exon 3 of 8	NP_110403.2	Q9H171-1
	ZBP1	NM_001160417.2		c.262G>T	p.Glu88*	stop_gained splice_region	Exon 3 of 8	NP_001153889.1
	ZBP1	NM_001160418.2		c.37G>T	p.Glu13*	stop_gained splice_region	Exon 2 of 7	NP_001153890.1	Q9H171-7

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZBP1	ENST00000371173.8	TSL:1 MANE Select	c.262G>T	p.Glu88*	stop_gained splice_region	Exon 3 of 8	ENSP00000360215.3	Q9H171-1
	ZBP1	ENST00000395822.7	TSL:2	c.37G>T	p.Glu13*	stop_gained splice_region	Exon 2 of 7	ENSP00000379167.3	Q9H171-7
	ZBP1	ENST00000857154.1		c.37G>T	p.Glu13*	stop_gained splice_region	Exon 2 of 7	ENSP00000527213.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 6.85e-7 AC: 1 AN: 1460024 Hom.: 0 Cov.: 47 AF XY: 0.00000138 AC XY: 1 AN XY: 726386

African (AFR) AF: 0.00 AC: 0 AN: 33324

American (AMR) AF: 0.00 AC: 0 AN: 44328

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26028

East Asian (EAS) AF: 0.00 AC: 0 AN: 39588

South Asian (SAS) AF: 0.00 AC: 0 AN: 86072

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53392

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5746

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1111252

Other (OTH) AF: 0.0000166 AC: 1 AN: 60294

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Uncertain	0.16	D
BayesDel_noAF	Uncertain	-0.010
CADD	Pathogenic	32
DANN	Uncertain	0.97
Eigen	Benign	-0.13
Eigen_PC	Benign	-0.55
FATHMM_MKL	Benign	0.012	N
PhyloP100		-0.39
Vest4		0.37
GERP RS		-1.1
Mutation Taster		=76/124	disease causing (fs/PTC)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.34		Details are displayed if max score is > 0.2
DS_AG_spliceai		0.34		Position offset: -3

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs2073145; hg19: chr20-56190634;