7-28135367-T-C

Variant names:

• chr7-28135367-T-C
• rs67250450
• NM_175061.4:c.115+45096A>G

Variant summary

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

The NM_175061.4(JAZF1):​c.115+45096A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.32 in 152,170 control chromosomes in the GnomAD database, including 9,847 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 0.32 (9847 hom., cov: 33)
• Consequence: JAZF1 NM_175061.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.134
• Publications: 38 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=-0.82).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.943 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_175061.4. 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
	JAZF1	NM_175061.4	MANE Select	c.115+45096A>G		intron	N/A	NP_778231.2	Q86VZ6-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	JAZF1	ENST00000283928.10	TSL:1 MANE Select	c.115+45096A>G		intron	N/A	ENSP00000283928.5	Q86VZ6-1
	JAZF1	ENST00000900291.1		c.115+45096A>G		intron	N/A	ENSP00000570350.1
	JAZF1	ENST00000919133.1		c.115+45096A>G		intron	N/A	ENSP00000589192.1

Frequencies

GnomAD3 genomes AF: 0.319 AC: 48553 AN: 152052 Hom.: 9815 Cov.: 33

Gnomad AFR AF: 0.411

Gnomad AMI AF: 0.252

Gnomad AMR AF: 0.390

Gnomad ASJ AF: 0.279

Gnomad EAS AF: 0.966

Gnomad SAS AF: 0.514

Gnomad FIN AF: 0.178

Gnomad MID AF: 0.256

Gnomad NFE AF: 0.210

Gnomad OTH AF: 0.308

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

GnomAD4 genome AF: 0.320 AC: 48635 AN: 152170 Hom.: 9847 Cov.: 33 AF XY: 0.327 AC XY: 24293 AN XY: 74404

African (AFR) AF: 0.412 AC: 17083 AN: 41492

American (AMR) AF: 0.390 AC: 5959 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.279 AC: 968 AN: 3472

East Asian (EAS) AF: 0.966 AC: 4997 AN: 5174

South Asian (SAS) AF: 0.513 AC: 2475 AN: 4826

European-Finnish (FIN) AF: 0.178 AC: 1886 AN: 10600

Middle Eastern (MID) AF: 0.259 AC: 76 AN: 294

European-Non Finnish (NFE) AF: 0.210 AC: 14300 AN: 68014

Other (OTH) AF: 0.312 AC: 661 AN: 2116

Alfa AF: 0.273 Hom.: 13387

Bravo AF: 0.344

Asia WGS AF: 0.716 AC: 2488 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	2.4
DANN	Benign	0.66
PhyloP100		0.13
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: rs67250450; hg19: chr7-28174986; COSMIC: COSV52240109;