rs714932

Variant names:

• chr5-32371672-G-A
• rs714932
• NM_016107.5:c.2836-7397C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_016107.5(ZFR):​c.2836-7397C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.283 in 151,614 control chromosomes in the GnomAD database, including 6,722 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 0.28 (6722 hom., cov: 31)
• Consequence: ZFR NM_016107.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.226
• Publications: 1 publications found

Genes affected

ZFR (HGNC:17277): (zinc finger RNA binding protein) This gene encodes an RNA-binding protein characterized by its DZF (domain associated with zinc fingers) domain. The encoded protein may play a role in the nucleocytoplasmic shuttling of another RNA-binding protein, Staufen homolog 2, in neurons. Expression of this gene is regulated through alternative polyadenylation that mediates differential microRNA targeting. Elevated expression of this gene has been observed in human patients with pancreatic cancer and knockdown of this gene may result in reduced viability and invasion of pancreatic cancer cells. [provided by RefSeq, Sep 2016]

ZFR Gene-Disease associations (from GenCC):

• autosomal recessive spastic paraplegia type 71

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
• hereditary spastic paraplegia

  Inheritance: AR Classification: LIMITED Submitted by: Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.336 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_016107.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZFR	NM_016107.5	MANE Select	c.2836-7397C>T		intron	N/A	NP_057191.2
	ZFR	NR_144318.2		n.2820-7397C>T		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZFR	ENST00000265069.13	TSL:1 MANE Select	c.2836-7397C>T		intron	N/A	ENSP00000265069.8	Q96KR1
	ZFR	ENST00000510369.5	TSL:1	n.254-7397C>T		intron	N/A
	ZFR	ENST00000956812.1		c.2836-109C>T		intron	N/A	ENSP00000626871.1

Frequencies

GnomAD3 genomes AF: 0.284 AC: 42963 AN: 151498 Hom.: 6729 Cov.: 31

Gnomad AFR AF: 0.162

Gnomad AMI AF: 0.272

Gnomad AMR AF: 0.321

Gnomad ASJ AF: 0.438

Gnomad EAS AF: 0.241

Gnomad SAS AF: 0.315

Gnomad FIN AF: 0.288

Gnomad MID AF: 0.443

Gnomad NFE AF: 0.340

Gnomad OTH AF: 0.332

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

GnomAD4 genome AF: 0.283 AC: 42970 AN: 151614 Hom.: 6722 Cov.: 31 AF XY: 0.284 AC XY: 21030 AN XY: 74066

African (AFR) AF: 0.162 AC: 6717 AN: 41430

American (AMR) AF: 0.320 AC: 4877 AN: 15246

Ashkenazi Jewish (ASJ) AF: 0.438 AC: 1514 AN: 3460

East Asian (EAS) AF: 0.240 AC: 1241 AN: 5164

South Asian (SAS) AF: 0.317 AC: 1522 AN: 4806

European-Finnish (FIN) AF: 0.288 AC: 2988 AN: 10368

Middle Eastern (MID) AF: 0.435 AC: 127 AN: 292

European-Non Finnish (NFE) AF: 0.340 AC: 23033 AN: 67838

Other (OTH) AF: 0.335 AC: 704 AN: 2102

Alfa AF: 0.323 Hom.: 10587

Bravo AF: 0.280

Asia WGS AF: 0.292 AC: 1011 AN: 3466

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	5.2
DANN	Benign	0.65
PhyloP100		0.23
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: rs714932; hg19: chr5-32371778;