rs849134

Variant names:

• chr7-28156603-A-G
• rs849134
• NM_175061.4:c.115+23860T>C

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+23860T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.405 in 152,036 control chromosomes in the GnomAD database, including 13,415 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 0.40 (13415 hom., cov: 32)
• Consequence: JAZF1 NM_175061.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.655
• Publications: 89 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=-0.88).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.494 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
JAZF1	NM_175061.4	c.115+23860T>C		intron_variant	Intron 1 of 4	ENST00000283928.10	NP_778231.2
JAZF1	XM_047420024.1	c.115+23860T>C		intron_variant	Intron 1 of 3		XP_047275980.1
JAZF1	XM_047420026.1	c.-78+23227T>C		intron_variant	Intron 1 of 4		XP_047275982.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
JAZF1	ENST00000283928.10	c.115+23860T>C		intron_variant	Intron 1 of 4	1	NM_175061.4	ENSP00000283928.5
JAZF1	ENST00000452993.5	n.115+23860T>C		intron_variant	Intron 1 of 4	4		ENSP00000415984.1
JAZF1	ENST00000454041.1	n.170+23860T>C		intron_variant	Intron 1 of 3	5
JAZF1	ENST00000649905.1	n.115+23860T>C		intron_variant	Intron 1 of 5			ENSP00000497321.1

Frequencies

GnomAD3 genomes AF: 0.405 AC: 61568 AN: 151918 Hom.: 13416 Cov.: 32

Gnomad AFR AF: 0.255

Gnomad AMI AF: 0.480

Gnomad AMR AF: 0.422

Gnomad ASJ AF: 0.542

Gnomad EAS AF: 0.225

Gnomad SAS AF: 0.270

Gnomad FIN AF: 0.469

Gnomad MID AF: 0.424

Gnomad NFE AF: 0.498

Gnomad OTH AF: 0.420

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

GnomAD4 genome AF: 0.405 AC: 61570 AN: 152036 Hom.: 13415 Cov.: 32 AF XY: 0.399 AC XY: 29666 AN XY: 74286

African (AFR) AF: 0.254 AC: 10544 AN: 41476

American (AMR) AF: 0.421 AC: 6438 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.542 AC: 1880 AN: 3468

East Asian (EAS) AF: 0.225 AC: 1165 AN: 5170

South Asian (SAS) AF: 0.271 AC: 1303 AN: 4810

European-Finnish (FIN) AF: 0.469 AC: 4953 AN: 10554

Middle Eastern (MID) AF: 0.418 AC: 123 AN: 294

European-Non Finnish (NFE) AF: 0.498 AC: 33850 AN: 67960

Other (OTH) AF: 0.414 AC: 876 AN: 2114

Alfa AF: 0.456 Hom.: 50856

Bravo AF: 0.396

Asia WGS AF: 0.249 AC: 868 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.20
DANN	Benign	0.26
PhyloP100		-0.66
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: rs849134; hg19: chr7-28196222;