11-58614213-A-G

Variant names:

• chr11-58614213-A-G
• rs1938596
• NM_053023.5:c.988-16A>G

Variant summary

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

The NM_053023.5(ZFP91):​c.988-16A>G variant causes a 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 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.16
• Publications: 9 publications found

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]

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_053023.5. 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
	ZFP91	NM_053023.5	MANE Select	c.988-16A>G		intron	N/A	NP_444251.1	Q96JP5-1
	ZFP91	NM_001197051.2		c.985-16A>G		intron	N/A	NP_001183980.1
	ZFP91-CNTF	NR_024091.1		n.1156-16A>G		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZFP91	ENST00000316059.7	TSL:1 MANE Select	c.988-16A>G		intron	N/A	ENSP00000339030.5	Q96JP5-1
	ZFP91-CNTF	ENST00000389919.8	TSL:2	n.988-16A>G		intron	N/A	ENSP00000455911.1
	ZFP91	ENST00000870367.1		c.988-16A>G		intron	N/A	ENSP00000540426.1

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

GnomAD2 exomes AF: 0.444 AC: 91526 AN: 206086 AF XY: 0.444

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 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

African (AFR) AF: 0.666 AC: 19552 AN: 29366

American (AMR) AF: 0.385 AC: 12441 AN: 32308

Ashkenazi Jewish (ASJ) AF: 0.410 AC: 9499 AN: 23196

East Asian (EAS) AF: 0.355 AC: 13380 AN: 37664

South Asian (SAS) AF: 0.463 AC: 32924 AN: 71106

European-Finnish (FIN) AF: 0.510 AC: 25317 AN: 49620

Middle Eastern (MID) AF: 0.528 AC: 2826 AN: 5350

European-Non Finnish (NFE) AF: 0.420 AC: 439363 AN: 1047252

Other (OTH) AF: 0.429 AC: 23826 AN: 55558

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

African (AFR) AF: 0.655 AC: 26991 AN: 41234

American (AMR) AF: 0.432 AC: 6556 AN: 15162

Ashkenazi Jewish (ASJ) AF: 0.420 AC: 1456 AN: 3464

East Asian (EAS) AF: 0.332 AC: 1703 AN: 5132

South Asian (SAS) AF: 0.466 AC: 2230 AN: 4784

European-Finnish (FIN) AF: 0.522 AC: 5417 AN: 10376

Middle Eastern (MID) AF: 0.589 AC: 172 AN: 292

European-Non Finnish (NFE) AF: 0.424 AC: 28705 AN: 67732

Other (OTH) AF: 0.471 AC: 986 AN: 2092

Alfa AF: 0.452 Hom.: 6010

Bravo AF: 0.490

Asia WGS AF: 0.409 AC: 1420 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.087
DANN	Benign	0.14
PhyloP100		-1.2
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
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: rs1938596; hg19: chr11-58381686; COSMIC: COSV60157982; COSMIC: COSV60157982;