7-28140937-T-C

Variant names:

• chr7-28140937-T-C
• rs864745
• NM_175061.4:c.115+39526A>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+39526A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.409 in 152,152 control chromosomes in the GnomAD database, including 13,752 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 0.41 (13752 hom., cov: 33)
• Consequence: JAZF1 NM_175061.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.76
• Publications: 325 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=-0.93).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.498 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
JAZF1	NM_175061.4	c.115+39526A>G		intron_variant	Intron 1 of 4	ENST00000283928.10	NP_778231.2
JAZF1	XM_047420024.1	c.115+39526A>G		intron_variant	Intron 1 of 3		XP_047275980.1
JAZF1	XM_047420026.1	c.-78+38893A>G		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+39526A>G		intron_variant	Intron 1 of 4	1	NM_175061.4	ENSP00000283928.5
JAZF1	ENST00000452993.5	n.115+39526A>G		intron_variant	Intron 1 of 4	4		ENSP00000415984.1
JAZF1	ENST00000454041.1	n.170+39526A>G		intron_variant	Intron 1 of 3	5
JAZF1	ENST00000649905.1	n.116-39133A>G		intron_variant	Intron 1 of 5			ENSP00000497321.1

Frequencies

GnomAD3 genomes AF: 0.410 AC: 62282 AN: 152034 Hom.: 13752 Cov.: 33

Gnomad AFR AF: 0.255

Gnomad AMI AF: 0.482

Gnomad AMR AF: 0.424

Gnomad ASJ AF: 0.543

Gnomad EAS AF: 0.226

Gnomad SAS AF: 0.270

Gnomad FIN AF: 0.497

Gnomad MID AF: 0.424

Gnomad NFE AF: 0.503

Gnomad OTH AF: 0.424

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

GnomAD4 genome AF: 0.409 AC: 62286 AN: 152152 Hom.: 13752 Cov.: 33 AF XY: 0.404 AC XY: 30082 AN XY: 74374

African (AFR) AF: 0.254 AC: 10556 AN: 41506

American (AMR) AF: 0.424 AC: 6480 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.543 AC: 1884 AN: 3470

East Asian (EAS) AF: 0.226 AC: 1171 AN: 5178

South Asian (SAS) AF: 0.270 AC: 1302 AN: 4820

European-Finnish (FIN) AF: 0.497 AC: 5252 AN: 10564

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

European-Non Finnish (NFE) AF: 0.503 AC: 34194 AN: 68012

Other (OTH) AF: 0.418 AC: 884 AN: 2114

Alfa AF: 0.461 Hom.: 52436

Bravo AF: 0.398

Asia WGS AF: 0.249 AC: 870 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.059
DANN	Benign	0.41
PhyloP100		-1.8
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: rs864745; hg19: chr7-28180556;