rs849141

Variant names:

• chr7-28145472-A-G
• rs849141
• NM_175061.4:c.115+34991T>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+34991T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.783 in 152,134 control chromosomes in the GnomAD database, including 47,294 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 (47294 hom., cov: 32)
• Consequence: JAZF1 NM_175061.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0100
• 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=-0.88).
• 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+34991T>C		intron_variant	Intron 1 of 4	ENST00000283928.10	NP_778231.2
JAZF1	XM_047420024.1	c.115+34991T>C		intron_variant	Intron 1 of 3		XP_047275980.1
JAZF1	XM_047420026.1	c.-78+34358T>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+34991T>C		intron_variant	Intron 1 of 4	1	NM_175061.4	ENSP00000283928.5
JAZF1	ENST00000452993.5	n.115+34991T>C		intron_variant	Intron 1 of 4	4		ENSP00000415984.1
JAZF1	ENST00000454041.1	n.170+34991T>C		intron_variant	Intron 1 of 3	5
JAZF1	ENST00000649905.1	n.115+34991T>C		intron_variant	Intron 1 of 5			ENSP00000497321.1

Frequencies

GnomAD3 genomes AF: 0.783 AC: 119049 AN: 152016 Hom.: 47236 Cov.: 32

Gnomad AFR AF: 0.879

Gnomad AMI AF: 0.747

Gnomad AMR AF: 0.829

Gnomad ASJ AF: 0.817

Gnomad EAS AF: 0.977

Gnomad SAS AF: 0.761

Gnomad FIN AF: 0.678

Gnomad MID AF: 0.699

Gnomad NFE AF: 0.717

Gnomad OTH AF: 0.766

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

GnomAD4 genome AF: 0.783 AC: 119163 AN: 152134 Hom.: 47294 Cov.: 32 AF XY: 0.782 AC XY: 58175 AN XY: 74356

African (AFR) AF: 0.879 AC: 36517 AN: 41544

American (AMR) AF: 0.830 AC: 12686 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.817 AC: 2836 AN: 3470

East Asian (EAS) AF: 0.977 AC: 5052 AN: 5170

South Asian (SAS) AF: 0.760 AC: 3663 AN: 4822

European-Finnish (FIN) AF: 0.678 AC: 7171 AN: 10570

Middle Eastern (MID) AF: 0.697 AC: 205 AN: 294

European-Non Finnish (NFE) AF: 0.717 AC: 48745 AN: 67960

Other (OTH) AF: 0.764 AC: 1610 AN: 2106

Alfa AF: 0.746 Hom.: 199278

Bravo AF: 0.803

Asia WGS AF: 0.889 AC: 3094 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	2.5
DANN	Benign	0.79
PhyloP100		0.010
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: rs849141; hg19: chr7-28185091;