rs618923

Positions:

• chr11-116783443-A-G

Variant summary

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

The ENST00000227322.8(ZPR1):​c.981+87T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.22 in 1,191,872 control chromosomes in the GnomAD database, including 31,695 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 0.19 (3358 hom., cov: 32)
  • Exomes 𝑓: 0.22 (28337 hom.)
• Consequence: ZPR1 ENST00000227322.8 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.633

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=-0.82).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.251 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZPR1	NM_003904.5	c.981+87T>C		intron_variant		ENST00000227322.8	NP_003895.1
ZPR1	NM_001317086.2	c.819+87T>C		intron_variant			NP_001304015.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZPR1	ENST00000227322.8	c.981+87T>C		intron_variant		1	NM_003904.5	ENSP00000227322	P1
ZPR1	ENST00000429220.5	c.760+87T>C		intron_variant		5		ENSP00000394495
ZPR1	ENST00000444935.5	c.980+87T>C		intron_variant		5		ENSP00000390391
ZPR1	ENST00000449430.1	c.*184+87T>C		intron_variant, NMD_transcript_variant		3		ENSP00000415505

Frequencies

GnomAD3 genomes AF: 0.195 AC: 29600 AN: 151976 Hom.: 3352 Cov.: 32

Gnomad AFR AF: 0.119

Gnomad AMI AF: 0.267

Gnomad AMR AF: 0.172

Gnomad ASJ AF: 0.252

Gnomad EAS AF: 0.00366

Gnomad SAS AF: 0.131

Gnomad FIN AF: 0.236

Gnomad MID AF: 0.212

Gnomad NFE AF: 0.255

Gnomad OTH AF: 0.206

GnomAD4 exome AF: 0.224 AC: 232781 AN: 1039778 Hom.: 28337 AF XY: 0.224 AC XY: 119314 AN XY: 532980

Gnomad4 AFR exome AF: 0.117

Gnomad4 AMR exome AF: 0.136

Gnomad4 ASJ exome AF: 0.261

Gnomad4 EAS exome AF: 0.000901

Gnomad4 SAS exome AF: 0.147

Gnomad4 FIN exome AF: 0.236

Gnomad4 NFE exome AF: 0.250

Gnomad4 OTH exome AF: 0.217

GnomAD4 genome AF: 0.195 AC: 29628 AN: 152094 Hom.: 3358 Cov.: 32 AF XY: 0.192 AC XY: 14281 AN XY: 74360

Gnomad4 AFR AF: 0.119

Gnomad4 AMR AF: 0.172

Gnomad4 ASJ AF: 0.252

Gnomad4 EAS AF: 0.00366

Gnomad4 SAS AF: 0.132

Gnomad4 FIN AF: 0.236

Gnomad4 NFE AF: 0.255

Gnomad4 OTH AF: 0.204

Alfa AF: 0.227 Hom.: 2084

Bravo AF: 0.184

Asia WGS AF: 0.0720 AC: 250 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	4.4
DANN	Benign	0.70

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: rs618923; hg19: chr11-116654159; COSMIC: COSV57065023; COSMIC: COSV57065023;