11-116786845-C-T

Position:

• chr11-116786845-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.424+124G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.743 in 818,886 control chromosomes in the GnomAD database, including 230,058 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 0.72 (40541 hom., cov: 33)
  • Exomes 𝑓: 0.75 (189517 hom.)
• Consequence: ZPR1 NM_003904.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.152

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=-0.76).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.791 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ZPR1	NM_003904.5	c.424+124G>A		intron_variant		ENST00000227322.8
ZPR1	NM_001317086.2	c.262+124G>A		intron_variant
ZPR1	XM_047427804.1	c.424+124G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ZPR1	ENST00000227322.8	c.424+124G>A		intron_variant		1	NM_003904.5	P1

Frequencies

GnomAD3 genomes AF: 0.724 AC: 110053 AN: 151940 Hom.: 40528 Cov.: 33

Gnomad AFR AF: 0.663

Gnomad AMI AF: 0.721

Gnomad AMR AF: 0.596

Gnomad ASJ AF: 0.756

Gnomad EAS AF: 0.591

Gnomad SAS AF: 0.670

Gnomad FIN AF: 0.769

Gnomad MID AF: 0.661

Gnomad NFE AF: 0.797

Gnomad OTH AF: 0.707

GnomAD4 exome AF: 0.747 AC: 498278 AN: 666828 Hom.: 189517 AF XY: 0.747 AC XY: 263938 AN XY: 353194

Gnomad4 AFR exome AF: 0.666

Gnomad4 AMR exome AF: 0.512

Gnomad4 ASJ exome AF: 0.763

Gnomad4 EAS exome AF: 0.514

Gnomad4 SAS exome AF: 0.671

Gnomad4 FIN exome AF: 0.763

Gnomad4 NFE exome AF: 0.800

Gnomad4 OTH exome AF: 0.742

GnomAD4 genome AF: 0.724 AC: 110104 AN: 152058 Hom.: 40541 Cov.: 33 AF XY: 0.717 AC XY: 53281 AN XY: 74328

Gnomad4 AFR AF: 0.663

Gnomad4 AMR AF: 0.595

Gnomad4 ASJ AF: 0.756

Gnomad4 EAS AF: 0.590

Gnomad4 SAS AF: 0.668

Gnomad4 FIN AF: 0.769

Gnomad4 NFE AF: 0.797

Gnomad4 OTH AF: 0.704

Alfa AF: 0.751 Hom.: 14270

Bravo AF: 0.709

Asia WGS AF: 0.603 AC: 2099 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.76
CADD	Benign	7.3
DANN	Benign	0.71

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

Publications

LitVar

Other links and lift over

dbSNP: rs3741298; hg19: chr11-116657561;