rs12154248

Variant names:

• chr7-28152756-C-T
• rs12154248
• NM_175061.4:c.115+27707G>A

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+27707G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.107 in 151,918 control chromosomes in the GnomAD database, including 1,400 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 0.11 (1400 hom., cov: 32)
• Consequence: JAZF1 NM_175061.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.415
• Publications: 8 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=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.458 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
JAZF1	NM_175061.4	c.115+27707G>A		intron_variant	Intron 1 of 4	ENST00000283928.10	NP_778231.2
JAZF1	XM_047420024.1	c.115+27707G>A		intron_variant	Intron 1 of 3		XP_047275980.1
JAZF1	XM_047420026.1	c.-78+27074G>A		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+27707G>A		intron_variant	Intron 1 of 4	1	NM_175061.4	ENSP00000283928.5
JAZF1	ENST00000452993.5	n.115+27707G>A		intron_variant	Intron 1 of 4	4		ENSP00000415984.1
JAZF1	ENST00000454041.1	n.170+27707G>A		intron_variant	Intron 1 of 3	5
JAZF1	ENST00000649905.1	n.115+27707G>A		intron_variant	Intron 1 of 5			ENSP00000497321.1

Frequencies

GnomAD3 genomes AF: 0.107 AC: 16203 AN: 151800 Hom.: 1394 Cov.: 32

Gnomad AFR AF: 0.0518

Gnomad AMI AF: 0.155

Gnomad AMR AF: 0.151

Gnomad ASJ AF: 0.149

Gnomad EAS AF: 0.474

Gnomad SAS AF: 0.196

Gnomad FIN AF: 0.106

Gnomad MID AF: 0.118

Gnomad NFE AF: 0.0932

Gnomad OTH AF: 0.111

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

GnomAD4 genome AF: 0.107 AC: 16233 AN: 151918 Hom.: 1400 Cov.: 32 AF XY: 0.110 AC XY: 8179 AN XY: 74220

African (AFR) AF: 0.0520 AC: 2156 AN: 41426

American (AMR) AF: 0.151 AC: 2310 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.149 AC: 516 AN: 3470

East Asian (EAS) AF: 0.474 AC: 2444 AN: 5156

South Asian (SAS) AF: 0.196 AC: 941 AN: 4804

European-Finnish (FIN) AF: 0.106 AC: 1112 AN: 10510

Middle Eastern (MID) AF: 0.116 AC: 34 AN: 292

European-Non Finnish (NFE) AF: 0.0932 AC: 6332 AN: 67970

Other (OTH) AF: 0.117 AC: 247 AN: 2106

Alfa AF: 0.109 Hom.: 642

Bravo AF: 0.109

Asia WGS AF: 0.304 AC: 1055 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	1.9
DANN	Benign	0.55
PhyloP100		-0.41
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: rs12154248; hg19: chr7-28192375;