7-27976715-T-C

Variant names:

• chr7-27976715-T-C
• rs38504
• NM_175061.4:c.188+15194A>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.188+15194A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.823 in 151,948 control chromosomes in the GnomAD database, including 52,135 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 0.82 (52135 hom., cov: 30)
• Consequence: JAZF1 NM_175061.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0190
• 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 (AFR) allele frequency at 95% confidence interval = 0.935 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
JAZF1	NM_175061.4	c.188+15194A>G		intron_variant	Intron 2 of 4	ENST00000283928.10	NP_778231.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
JAZF1	ENST00000283928.10	c.188+15194A>G		intron_variant	Intron 2 of 4	1	NM_175061.4	ENSP00000283928.5

Frequencies

GnomAD3 genomes AF: 0.823 AC: 124998 AN: 151830 Hom.: 52083 Cov.: 30

Gnomad AFR AF: 0.942

Gnomad AMI AF: 0.630

Gnomad AMR AF: 0.774

Gnomad ASJ AF: 0.731

Gnomad EAS AF: 0.535

Gnomad SAS AF: 0.766

Gnomad FIN AF: 0.799

Gnomad MID AF: 0.816

Gnomad NFE AF: 0.799

Gnomad OTH AF: 0.816

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

GnomAD4 genome AF: 0.823 AC: 125105 AN: 151948 Hom.: 52135 Cov.: 30 AF XY: 0.821 AC XY: 60936 AN XY: 74262

African (AFR) AF: 0.942 AC: 39104 AN: 41492

American (AMR) AF: 0.774 AC: 11816 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.731 AC: 2529 AN: 3462

East Asian (EAS) AF: 0.535 AC: 2757 AN: 5156

South Asian (SAS) AF: 0.766 AC: 3681 AN: 4804

European-Finnish (FIN) AF: 0.799 AC: 8389 AN: 10502

Middle Eastern (MID) AF: 0.820 AC: 241 AN: 294

European-Non Finnish (NFE) AF: 0.799 AC: 54302 AN: 67954

Other (OTH) AF: 0.811 AC: 1713 AN: 2112

Alfa AF: 0.798 Hom.: 82258

Bravo AF: 0.820

Asia WGS AF: 0.661 AC: 2298 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	5.3
DANN	Benign	0.41
PhyloP100		-0.019
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: rs38504; hg19: chr7-28016334; COSMIC: COSV52234354;