7-28149792-T-C

Variant names:

• chr7-28149792-T-C
• rs1635852
• NM_175061.4:c.115+30671A>G

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_175061.4(JAZF1):​c.115+30671A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.416 in 152,036 control chromosomes in the GnomAD database, including 14,052 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.42 (14052 hom., cov: 32)
• Consequence: JAZF1 NM_175061.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.278
• Publications: 112 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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BP6: Variant 7-28149792-T-C is Benign according to our data. Variant chr7-28149792-T-C is described in ClinVar as Benign. ClinVar VariationId is 1287219.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.5 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
JAZF1	NM_175061.4	c.115+30671A>G		intron_variant	Intron 1 of 4	ENST00000283928.10	NP_778231.2
JAZF1	XM_047420024.1	c.115+30671A>G		intron_variant	Intron 1 of 3		XP_047275980.1
JAZF1	XM_047420026.1	c.-78+30038A>G		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+30671A>G		intron_variant	Intron 1 of 4	1	NM_175061.4	ENSP00000283928.5
JAZF1	ENST00000452993.5	n.115+30671A>G		intron_variant	Intron 1 of 4	4		ENSP00000415984.1
JAZF1	ENST00000454041.1	n.170+30671A>G		intron_variant	Intron 1 of 3	5
JAZF1	ENST00000649905.1	n.115+30671A>G		intron_variant	Intron 1 of 5			ENSP00000497321.1

Frequencies

GnomAD3 genomes AF: 0.416 AC: 63232 AN: 151918 Hom.: 14049 Cov.: 32

Gnomad AFR AF: 0.277

Gnomad AMI AF: 0.480

Gnomad AMR AF: 0.424

Gnomad ASJ AF: 0.557

Gnomad EAS AF: 0.226

Gnomad SAS AF: 0.275

Gnomad FIN AF: 0.488

Gnomad MID AF: 0.427

Gnomad NFE AF: 0.504

Gnomad OTH AF: 0.427

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

GnomAD4 genome AF: 0.416 AC: 63246 AN: 152036 Hom.: 14052 Cov.: 32 AF XY: 0.411 AC XY: 30514 AN XY: 74304

African (AFR) AF: 0.277 AC: 11479 AN: 41470

American (AMR) AF: 0.424 AC: 6469 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.557 AC: 1932 AN: 3466

East Asian (EAS) AF: 0.226 AC: 1169 AN: 5168

South Asian (SAS) AF: 0.275 AC: 1328 AN: 4822

European-Finnish (FIN) AF: 0.488 AC: 5161 AN: 10572

Middle Eastern (MID) AF: 0.422 AC: 124 AN: 294

European-Non Finnish (NFE) AF: 0.504 AC: 34259 AN: 67958

Other (OTH) AF: 0.422 AC: 889 AN: 2108

Alfa AF: 0.471 Hom.: 72362

Bravo AF: 0.406

Asia WGS AF: 0.253 AC: 882 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Apr 28, 2020

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is associated with the following publications: (PMID: 23328127)

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	7.0
DANN	Benign	0.53
PhyloP100		0.28
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs1635852; hg19: chr7-28189411;