rs948562

Positions:

• chr11-58580292-A-G

Variant summary

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

The NM_053023.5(ZFP91):​c.341+670A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.148 in 152,076 control chromosomes in the GnomAD database, including 1,880 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 0.15 (1880 hom., cov: 32)
• Consequence: ZFP91 NM_053023.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.500

Genes affected

ZFP91 (HGNC:14983): (ZFP91 zinc finger protein, atypical E3 ubiquitin ligase) The protein encoded by this gene is a member of the zinc finger family of proteins. The gene product contains C2H2-type domains, which are the classical zinc finger domains found in numerous nucleic acid-binding proteins. This protein functions as a regulator of the non-canonical NF-kappaB pathway in lymphotoxin-beta receptor signaling. Alternative splicing results in multiple transcript variants. A read-through transcript variant composed of ZFP91 and the downstream CNTF gene sequence has been identified, but it is thought to be non-coding. Read-through transcription of ZFP91 and CNTF has also been observed in mouse. A ZFP91-related pseudogene has also been identified on chromosome 2. [provided by RefSeq, Oct 2010]

ZFP91-CNTF (HGNC:33441): (ZFP91-CNTF readthrough (NMD candidate)) This gene represents a read-through transcript composed of ZFP91 and CNTF sequence. This transcript is thought to be non-coding because it would be subject to nonsense-mediated mRNA decay (NMD). Read-through transcription of ZFP91 and CNTF has also been observed in mouse. [provided by RefSeq, Aug 2008]

ZFP91-CNTF (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.78).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.186 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZFP91	NM_053023.5	c.341+670A>G		intron_variant		ENST00000316059.7	NP_444251.1
ZFP91	NM_001197051.2	c.341+670A>G		intron_variant			NP_001183980.1
ZFP91-CNTF	NR_024091.1	n.509+670A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZFP91	ENST00000316059.7	c.341+670A>G		intron_variant		1	NM_053023.5	ENSP00000339030.5
ZFP91-CNTF	ENST00000389919.8	n.341+670A>G		intron_variant		2		ENSP00000455911.1

Frequencies

GnomAD3 genomes AF: 0.148 AC: 22522 AN: 151958 Hom.: 1878 Cov.: 32

Gnomad AFR AF: 0.0746

Gnomad AMI AF: 0.158

Gnomad AMR AF: 0.192

Gnomad ASJ AF: 0.147

Gnomad EAS AF: 0.135

Gnomad SAS AF: 0.173

Gnomad FIN AF: 0.216

Gnomad MID AF: 0.199

Gnomad NFE AF: 0.171

Gnomad OTH AF: 0.161

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

GnomAD4 genome AF: 0.148 AC: 22527 AN: 152076 Hom.: 1880 Cov.: 32 AF XY: 0.152 AC XY: 11265 AN XY: 74328

Gnomad4 AFR AF: 0.0744

Gnomad4 AMR AF: 0.192

Gnomad4 ASJ AF: 0.147

Gnomad4 EAS AF: 0.135

Gnomad4 SAS AF: 0.174

Gnomad4 FIN AF: 0.216

Gnomad4 NFE AF: 0.171

Gnomad4 OTH AF: 0.161

Alfa AF: 0.168 Hom.: 1532

Bravo AF: 0.142

Asia WGS AF: 0.120 AC: 417 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	1.4
DANN	Benign	0.57

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.13		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: rs948562; hg19: chr11-58347765;