7-28150327-A-G

Variant names:

• chr7-28150327-A-G
• rs1708299
• NM_175061.4:c.115+30136T>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+30136T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.775 in 152,140 control chromosomes in the GnomAD database, including 46,427 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 0.78 (46427 hom., cov: 32)
• Consequence: JAZF1 NM_175061.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0670
• Publications: 37 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=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.955 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
JAZF1	NM_175061.4	c.115+30136T>C		intron_variant	Intron 1 of 4	ENST00000283928.10	NP_778231.2
JAZF1	XM_047420024.1	c.115+30136T>C		intron_variant	Intron 1 of 3		XP_047275980.1
JAZF1	XM_047420026.1	c.-78+29503T>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+30136T>C		intron_variant	Intron 1 of 4	1	NM_175061.4	ENSP00000283928.5
JAZF1	ENST00000452993.5	n.115+30136T>C		intron_variant	Intron 1 of 4	4		ENSP00000415984.1
JAZF1	ENST00000454041.1	n.170+30136T>C		intron_variant	Intron 1 of 3	5
JAZF1	ENST00000649905.1	n.115+30136T>C		intron_variant	Intron 1 of 5			ENSP00000497321.1

Frequencies

GnomAD3 genomes AF: 0.775 AC: 117844 AN: 152022 Hom.: 46370 Cov.: 32

Gnomad AFR AF: 0.877

Gnomad AMI AF: 0.746

Gnomad AMR AF: 0.824

Gnomad ASJ AF: 0.814

Gnomad EAS AF: 0.977

Gnomad SAS AF: 0.761

Gnomad FIN AF: 0.650

Gnomad MID AF: 0.693

Gnomad NFE AF: 0.706

Gnomad OTH AF: 0.758

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

GnomAD4 genome AF: 0.775 AC: 117957 AN: 152140 Hom.: 46427 Cov.: 32 AF XY: 0.775 AC XY: 57603 AN XY: 74374

African (AFR) AF: 0.878 AC: 36441 AN: 41518

American (AMR) AF: 0.824 AC: 12601 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.814 AC: 2824 AN: 3468

East Asian (EAS) AF: 0.977 AC: 5061 AN: 5178

South Asian (SAS) AF: 0.760 AC: 3664 AN: 4820

European-Finnish (FIN) AF: 0.650 AC: 6875 AN: 10580

Middle Eastern (MID) AF: 0.690 AC: 203 AN: 294

European-Non Finnish (NFE) AF: 0.706 AC: 48011 AN: 67966

Other (OTH) AF: 0.756 AC: 1598 AN: 2114

Alfa AF: 0.739 Hom.: 127618

Bravo AF: 0.797

Asia WGS AF: 0.888 AC: 3090 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	3.4
DANN	Benign	0.80
PhyloP100		0.067
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: rs1708299; hg19: chr7-28189946;