chr11-116781585-C-T

Variant names:

• chr11-116781585-C-T
• rs4417316
• NM_003904.5:c.1179+573G>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.1179+573G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0937 in 152,220 control chromosomes in the GnomAD database, including 952 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 0.094 (952 hom., cov: 32)
• Consequence: ZPR1 NM_003904.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.63
• Publications: 16 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=-0.98).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.243 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZPR1	NM_003904.5	c.1179+573G>A		intron_variant	Intron 12 of 13	ENST00000227322.8	NP_003895.1
ZPR1	NM_001317086.2	c.1017+573G>A		intron_variant	Intron 11 of 12		NP_001304015.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZPR1	ENST00000227322.8	c.1179+573G>A		intron_variant	Intron 12 of 13	1	NM_003904.5	ENSP00000227322.3
ZPR1	ENST00000444935.5	c.1089+1334G>A		intron_variant	Intron 11 of 12	5		ENSP00000390391.1
ZPR1	ENST00000429220.5	c.957+573G>A		intron_variant	Intron 10 of 11	5		ENSP00000394495.1

Frequencies

GnomAD3 genomes AF: 0.0938 AC: 14265 AN: 152102 Hom.: 952 Cov.: 32

Gnomad AFR AF: 0.0403

Gnomad AMI AF: 0.0132

Gnomad AMR AF: 0.0976

Gnomad ASJ AF: 0.0795

Gnomad EAS AF: 0.247

Gnomad SAS AF: 0.256

Gnomad FIN AF: 0.162

Gnomad MID AF: 0.0949

Gnomad NFE AF: 0.0939

Gnomad OTH AF: 0.0798

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

GnomAD4 genome AF: 0.0937 AC: 14265 AN: 152220 Hom.: 952 Cov.: 32 AF XY: 0.100 AC XY: 7464 AN XY: 74408

African (AFR) AF: 0.0402 AC: 1671 AN: 41556

American (AMR) AF: 0.0978 AC: 1496 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.0795 AC: 276 AN: 3470

East Asian (EAS) AF: 0.247 AC: 1279 AN: 5170

South Asian (SAS) AF: 0.255 AC: 1232 AN: 4828

European-Finnish (FIN) AF: 0.162 AC: 1711 AN: 10568

Middle Eastern (MID) AF: 0.0918 AC: 27 AN: 294

European-Non Finnish (NFE) AF: 0.0939 AC: 6384 AN: 68012

Other (OTH) AF: 0.0837 AC: 177 AN: 2114

Alfa AF: 0.0758 Hom.: 134

Bravo AF: 0.0863

Asia WGS AF: 0.231 AC: 803 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	0.063
DANN	Benign	0.59
PhyloP100		-1.6
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: rs4417316; hg19: chr11-116652301;