NM_175061.4:c.189-8774G>A

Variant names:

• chr7-27904190-C-T
• rs193
• NM_175061.4:c.189-8774G>A

Variant summary

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

The NM_175061.4(JAZF1):​c.189-8774G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.369 in 152,046 control chromosomes in the GnomAD database, including 10,546 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 0.37 (10546 hom., cov: 32)
• Consequence: JAZF1 NM_175061.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.571
• Publications: 9 publications found

Genes affected

JAZF1 (HGNC:28917): (JAZF zinc finger 1) This gene encodes a nuclear protein with three C2H2-type zinc fingers, and functions as a transcriptional repressor. Chromosomal aberrations involving this gene are associated with endometrial stromal tumors. Alternatively spliced variants which encode different protein isoforms have been described; however, not all variants have been fully characterized [provided by RefSeq, Jul 2008]

JAZF1 Gene-Disease associations (from GenCC):

• systemic lupus erythematosus

  Inheritance: Unknown Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.476 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
JAZF1	NM_175061.4	c.189-8774G>A		intron_variant	Intron 2 of 4	ENST00000283928.10	NP_778231.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
JAZF1	ENST00000283928.10	c.189-8774G>A		intron_variant	Intron 2 of 4	1	NM_175061.4	ENSP00000283928.5

Frequencies

GnomAD3 genomes AF: 0.368 AC: 55984 AN: 151928 Hom.: 10528 Cov.: 32

Gnomad AFR AF: 0.380

Gnomad AMI AF: 0.350

Gnomad AMR AF: 0.454

Gnomad ASJ AF: 0.260

Gnomad EAS AF: 0.492

Gnomad SAS AF: 0.366

Gnomad FIN AF: 0.313

Gnomad MID AF: 0.350

Gnomad NFE AF: 0.348

Gnomad OTH AF: 0.361

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

GnomAD4 genome AF: 0.369 AC: 56052 AN: 152046 Hom.: 10546 Cov.: 32 AF XY: 0.371 AC XY: 27534 AN XY: 74314

African (AFR) AF: 0.380 AC: 15772 AN: 41484

American (AMR) AF: 0.455 AC: 6944 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.260 AC: 902 AN: 3470

East Asian (EAS) AF: 0.491 AC: 2537 AN: 5162

South Asian (SAS) AF: 0.365 AC: 1758 AN: 4812

European-Finnish (FIN) AF: 0.313 AC: 3304 AN: 10564

Middle Eastern (MID) AF: 0.366 AC: 107 AN: 292

European-Non Finnish (NFE) AF: 0.348 AC: 23643 AN: 67984

Other (OTH) AF: 0.365 AC: 767 AN: 2102

Alfa AF: 0.355 Hom.: 42899

Bravo AF: 0.376

Asia WGS AF: 0.406 AC: 1409 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.48
DANN	Benign	0.70
PhyloP100		-0.57
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: rs193; hg19: chr7-27943809;