rs1938596

chr11-58614213-A-Gchr11-58614213-A-T

Variant summary

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

The NM_053023.5(ZFP91):c.988-16A>G variant causes a splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.435 in 1,502,596 control chromosomes in the GnomAD database, including 145,799 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 0.49 (19218 hom., cov: 30)
  • Exomes 𝑓: 0.43 (126581 hom.)
• Consequence: ZFP91 NM_053023.5 splice_polypyrimidine_tract, intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.16

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:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.648 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ZFP91	NM_053023.5	c.988-16A>G		splice_polypyrimidine_tract_variant, intron_variant		ENST00000316059.7
ZFP91-CNTF	NR_024091.1	n.1156-16A>G		splice_polypyrimidine_tract_variant, intron_variant, non_coding_transcript_variant
ZFP91	NM_001197051.2	c.985-16A>G		splice_polypyrimidine_tract_variant, intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ZFP91	ENST00000316059.7	c.988-16A>G		splice_polypyrimidine_tract_variant, intron_variant		1	NM_053023.5	P1

Frequencies

GnomAD3 genomes AF: 0.493 AC: 74516 AN: 151060 Hom.: 19184 Cov.: 30

Gnomad AFR AF: 0.654

Gnomad AMI AF: 0.421

Gnomad AMR AF: 0.433

Gnomad ASJ AF: 0.420

Gnomad EAS AF: 0.332

Gnomad SAS AF: 0.466

Gnomad FIN AF: 0.522

Gnomad MID AF: 0.576

Gnomad NFE AF: 0.424

Gnomad OTH AF: 0.474

GnomAD3 exomes AF: 0.444 AC: 91526 AN: 206086 Hom.: 21292 AF XY: 0.444 AC XY: 49783 AN XY: 112248

Gnomad AFR exome AF: 0.657

Gnomad AMR exome AF: 0.376

Gnomad ASJ exome AF: 0.407

Gnomad EAS exome AF: 0.321

Gnomad SAS exome AF: 0.464

Gnomad FIN exome AF: 0.518

Gnomad NFE exome AF: 0.432

Gnomad OTH exome AF: 0.434

GnomAD4 exome AF: 0.429 AC: 579128 AN: 1351420 Hom.: 126581 Cov.: 21 AF XY: 0.429 AC XY: 286804 AN XY: 667792

Gnomad4 AFR exome AF: 0.666

Gnomad4 AMR exome AF: 0.385

Gnomad4 ASJ exome AF: 0.410

Gnomad4 EAS exome AF: 0.355

Gnomad4 SAS exome AF: 0.463

Gnomad4 FIN exome AF: 0.510

Gnomad4 NFE exome AF: 0.420

Gnomad4 OTH exome AF: 0.429

GnomAD4 genome AF: 0.493 AC: 74598 AN: 151176 Hom.: 19218 Cov.: 30 AF XY: 0.495 AC XY: 36552 AN XY: 73784

Gnomad4 AFR AF: 0.655

Gnomad4 AMR AF: 0.432

Gnomad4 ASJ AF: 0.420

Gnomad4 EAS AF: 0.332

Gnomad4 SAS AF: 0.466

Gnomad4 FIN AF: 0.522

Gnomad4 NFE AF: 0.424

Gnomad4 OTH AF: 0.471

Alfa AF: 0.451 Hom.: 3735

Bravo AF: 0.490

Asia WGS AF: 0.409 AC: 1420 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
Cadd	Benign	0.087
Dann	Benign	0.14
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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: rs1938596; hg19: chr11-58381686; COSMIC: COSV60157982; COSMIC: COSV60157982;