11-116782580-C-T

Variant names:

• chr11-116782580-C-T
• rs2075290
• NM_003904.5:c.1093-336G>A

Variant summary

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

The NM_003904.5(ZPR1):​c.1093-336G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.913 in 152,264 control chromosomes in the GnomAD database, including 63,710 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 0.91 (63710 hom., cov: 33)
• Consequence: ZPR1 NM_003904.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.17
• Publications: 73 publications found

Genes affected

ZPR1 (HGNC:13051): (ZPR1 zinc finger) The protein encoded by this gene is found in the cytoplasm of quiescent cells but translocates to the nucleolus in proliferating cells. The encoded protein interacts with survival motor neuron protein (SMN1) to enhance pre-mRNA splicing and to induce neuronal differentiation and axonal growth. Defects in this gene or the SMN1 gene can cause spinal muscular atrophy. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Nov 2015]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.934 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZPR1	NM_003904.5	c.1093-336G>A		intron_variant	Intron 11 of 13	ENST00000227322.8	NP_003895.1
ZPR1	NM_001317086.2	c.931-336G>A		intron_variant	Intron 10 of 12		NP_001304015.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZPR1	ENST00000227322.8	c.1093-336G>A		intron_variant	Intron 11 of 13	1	NM_003904.5	ENSP00000227322.3
ZPR1	ENST00000444935.5	c.1089+339G>A		intron_variant	Intron 11 of 12	5		ENSP00000390391.1
ZPR1	ENST00000429220.5	c.871-336G>A		intron_variant	Intron 9 of 11	5		ENSP00000394495.1
ZPR1	ENST00000449430.1	n.*296-336G>A		intron_variant	Intron 7 of 7	3		ENSP00000415505.1

Frequencies

GnomAD3 genomes AF: 0.913 AC: 138982 AN: 152146 Hom.: 63665 Cov.: 33

Gnomad AFR AF: 0.942

Gnomad AMI AF: 0.881

Gnomad AMR AF: 0.876

Gnomad ASJ AF: 0.898

Gnomad EAS AF: 0.753

Gnomad SAS AF: 0.807

Gnomad FIN AF: 0.916

Gnomad MID AF: 0.864

Gnomad NFE AF: 0.926

Gnomad OTH AF: 0.904

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.913 AC: 139083 AN: 152264 Hom.: 63710 Cov.: 33 AF XY: 0.910 AC XY: 67762 AN XY: 74456

African (AFR) AF: 0.942 AC: 39143 AN: 41562

American (AMR) AF: 0.876 AC: 13411 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.898 AC: 3117 AN: 3472

East Asian (EAS) AF: 0.752 AC: 3892 AN: 5174

South Asian (SAS) AF: 0.807 AC: 3894 AN: 4826

European-Finnish (FIN) AF: 0.916 AC: 9719 AN: 10612

Middle Eastern (MID) AF: 0.867 AC: 255 AN: 294

European-Non Finnish (NFE) AF: 0.926 AC: 62951 AN: 68000

Other (OTH) AF: 0.899 AC: 1903 AN: 2116

Alfa AF: 0.917 Hom.: 192409

Bravo AF: 0.912

Asia WGS AF: 0.797 AC: 2773 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.17
DANN	Benign	0.20
PhyloP100		-1.2
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		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: rs2075290; hg19: chr11-116653296;