chr11-116783719-C-T

Position:

• chr11-116783719-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.892-100G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.382 in 866,758 control chromosomes in the GnomAD database, including 66,815 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 0.33 (9416 hom., cov: 31)
  • Exomes 𝑓: 0.39 (57399 hom.)
• Consequence: ZPR1 NM_003904.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.642

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=-0.84).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.431 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ZPR1	NM_003904.5	c.892-100G>A		intron_variant		ENST00000227322.8
ZPR1	NM_001317086.2	c.730-100G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ZPR1	ENST00000227322.8	c.892-100G>A		intron_variant		1	NM_003904.5	P1
ZPR1	ENST00000429220.5	c.671-100G>A		intron_variant		5
ZPR1	ENST00000444935.5	c.891-100G>A		intron_variant		5
ZPR1	ENST00000449430.1	c.*95-100G>A		intron_variant, NMD_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.332 AC: 50415 AN: 151752 Hom.: 9424 Cov.: 31

Gnomad AFR AF: 0.184

Gnomad AMI AF: 0.392

Gnomad AMR AF: 0.278

Gnomad ASJ AF: 0.399

Gnomad EAS AF: 0.281

Gnomad SAS AF: 0.264

Gnomad FIN AF: 0.358

Gnomad MID AF: 0.301

Gnomad NFE AF: 0.435

Gnomad OTH AF: 0.333

GnomAD4 exome AF: 0.392 AC: 280346 AN: 714886 Hom.: 57399 AF XY: 0.389 AC XY: 147523 AN XY: 379720

Gnomad4 AFR exome AF: 0.182

Gnomad4 AMR exome AF: 0.252

Gnomad4 ASJ exome AF: 0.408

Gnomad4 EAS exome AF: 0.244

Gnomad4 SAS exome AF: 0.272

Gnomad4 FIN exome AF: 0.363

Gnomad4 NFE exome AF: 0.443

Gnomad4 OTH exome AF: 0.378

GnomAD4 genome AF: 0.332 AC: 50404 AN: 151872 Hom.: 9416 Cov.: 31 AF XY: 0.324 AC XY: 24028 AN XY: 74232

Gnomad4 AFR AF: 0.184

Gnomad4 AMR AF: 0.277

Gnomad4 ASJ AF: 0.399

Gnomad4 EAS AF: 0.279

Gnomad4 SAS AF: 0.264

Gnomad4 FIN AF: 0.358

Gnomad4 NFE AF: 0.435

Gnomad4 OTH AF: 0.329

Alfa AF: 0.344 Hom.: 2235

Bravo AF: 0.322

Asia WGS AF: 0.244 AC: 851 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	7.5
DANN	Benign	0.41

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs603446; hg19: chr11-116654435; COSMIC: COSV57062211; COSMIC: COSV57062211;