7-28149930-T-G

Variant names:

• chr7-28149930-T-G
• rs1635853
• NM_175061.4:c.115+30533A>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+30533A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.58 in 152,046 control chromosomes in the GnomAD database, including 25,825 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 0.58 (25825 hom., cov: 32)
• Consequence: JAZF1 NM_175061.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.36
• Publications: 15 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=-0.84).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.68 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
JAZF1	NM_175061.4	c.115+30533A>C		intron_variant	Intron 1 of 4	ENST00000283928.10	NP_778231.2
JAZF1	XM_047420024.1	c.115+30533A>C		intron_variant	Intron 1 of 3		XP_047275980.1
JAZF1	XM_047420026.1	c.-78+29900A>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+30533A>C		intron_variant	Intron 1 of 4	1	NM_175061.4	ENSP00000283928.5
JAZF1	ENST00000452993.5	n.115+30533A>C		intron_variant	Intron 1 of 4	4		ENSP00000415984.1
JAZF1	ENST00000454041.1	n.170+30533A>C		intron_variant	Intron 1 of 3	5
JAZF1	ENST00000649905.1	n.115+30533A>C		intron_variant	Intron 1 of 5			ENSP00000497321.1

Frequencies

GnomAD3 genomes AF: 0.580 AC: 88147 AN: 151928 Hom.: 25801 Cov.: 32

Gnomad AFR AF: 0.536

Gnomad AMI AF: 0.635

Gnomad AMR AF: 0.605

Gnomad ASJ AF: 0.701

Gnomad EAS AF: 0.699

Gnomad SAS AF: 0.466

Gnomad FIN AF: 0.576

Gnomad MID AF: 0.551

Gnomad NFE AF: 0.594

Gnomad OTH AF: 0.587

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

GnomAD4 genome AF: 0.580 AC: 88222 AN: 152046 Hom.: 25825 Cov.: 32 AF XY: 0.577 AC XY: 42859 AN XY: 74332

African (AFR) AF: 0.536 AC: 22227 AN: 41482

American (AMR) AF: 0.605 AC: 9252 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.701 AC: 2428 AN: 3466

East Asian (EAS) AF: 0.699 AC: 3614 AN: 5172

South Asian (SAS) AF: 0.466 AC: 2243 AN: 4814

European-Finnish (FIN) AF: 0.576 AC: 6090 AN: 10574

Middle Eastern (MID) AF: 0.544 AC: 160 AN: 294

European-Non Finnish (NFE) AF: 0.595 AC: 40392 AN: 67942

Other (OTH) AF: 0.587 AC: 1237 AN: 2106

Alfa AF: 0.574 Hom.: 14978

Bravo AF: 0.584

Asia WGS AF: 0.579 AC: 2012 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	0.46
DANN	Benign	0.66
PhyloP100		-1.4
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: rs1635853; hg19: chr7-28189549;