rs10486567

Positions:

• chr7-27936944-G-A
• chr7-27936944-G-C

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_175061.4(JAZF1):​c.189-41528C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.292 in 152,122 control chromosomes in the GnomAD database, including 7,730 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 0.29 (7730 hom., cov: 33)
• Consequence: JAZF1 NM_175061.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.568

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]

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.38).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.853 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
JAZF1	NM_175061.4	c.189-41528C>T		intron_variant		ENST00000283928.10	NP_778231.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
JAZF1	ENST00000283928.10	c.189-41528C>T		intron_variant		1	NM_175061.4	ENSP00000283928	P1

Frequencies

GnomAD3 genomes AF: 0.292 AC: 44361 AN: 152004 Hom.: 7718 Cov.: 33

Gnomad AFR AF: 0.285

Gnomad AMI AF: 0.235

Gnomad AMR AF: 0.405

Gnomad ASJ AF: 0.306

Gnomad EAS AF: 0.874

Gnomad SAS AF: 0.316

Gnomad FIN AF: 0.265

Gnomad MID AF: 0.231

Gnomad NFE AF: 0.229

Gnomad OTH AF: 0.292

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

GnomAD4 genome AF: 0.292 AC: 44396 AN: 152122 Hom.: 7730 Cov.: 33 AF XY: 0.299 AC XY: 22242 AN XY: 74382

Gnomad4 AFR AF: 0.285

Gnomad4 AMR AF: 0.406

Gnomad4 ASJ AF: 0.306

Gnomad4 EAS AF: 0.874

Gnomad4 SAS AF: 0.313

Gnomad4 FIN AF: 0.265

Gnomad4 NFE AF: 0.229

Gnomad4 OTH AF: 0.294

Alfa AF: 0.251 Hom.: 10205

Bravo AF: 0.308

Asia WGS AF: 0.565 AC: 1964 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.38
CADD	Benign	15
DANN	Benign	0.65

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

Publications

LitVar

Other links and lift over

dbSNP: rs10486567; hg19: chr7-27976563; COSMIC: COSV52232061;