rs12286037

Positions:

• chr11-116781491-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_003904.5(ZPR1):​c.1179+667G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.108 in 152,206 control chromosomes in the GnomAD database, including 1,181 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 0.11 (1181 hom., cov: 32)
• Consequence: ZPR1 NM_003904.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.28

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.0).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.197 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZPR1	NM_003904.5	c.1179+667G>A		intron_variant		ENST00000227322.8	NP_003895.1
ZPR1	NM_001317086.2	c.1017+667G>A		intron_variant			NP_001304015.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZPR1	ENST00000227322.8	c.1179+667G>A		intron_variant		1	NM_003904.5	ENSP00000227322.3
ZPR1	ENST00000444935.5	c.1089+1428G>A		intron_variant		5		ENSP00000390391.1
ZPR1	ENST00000429220.5	c.957+667G>A		intron_variant		5		ENSP00000394495.1

Frequencies

GnomAD3 genomes AF: 0.108 AC: 16380 AN: 152088 Hom.: 1177 Cov.: 32

Gnomad AFR AF: 0.201

Gnomad AMI AF: 0.126

Gnomad AMR AF: 0.135

Gnomad ASJ AF: 0.0859

Gnomad EAS AF: 0.000192

Gnomad SAS AF: 0.0429

Gnomad FIN AF: 0.0537

Gnomad MID AF: 0.133

Gnomad NFE AF: 0.0671

Gnomad OTH AF: 0.110

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

GnomAD4 genome AF: 0.108 AC: 16419 AN: 152206 Hom.: 1181 Cov.: 32 AF XY: 0.107 AC XY: 7926 AN XY: 74420

Gnomad4 AFR AF: 0.201

Gnomad4 AMR AF: 0.135

Gnomad4 ASJ AF: 0.0859

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.0432

Gnomad4 FIN AF: 0.0537

Gnomad4 NFE AF: 0.0671

Gnomad4 OTH AF: 0.109

Alfa AF: 0.0751 Hom.: 752

Bravo AF: 0.118

Asia WGS AF: 0.0400 AC: 141 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.14
DANN	Benign	0.58

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: rs12286037; hg19: chr11-116652207;