rs7834726

Positions:

• chr8-105785151-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_012082.4(ZFPM2):​c.533-3567T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0824 in 149,786 control chromosomes in the GnomAD database, including 1,767 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 0.082 (1767 hom., cov: 31)
  • Failed GnomAD Quality Control
• Consequence: ZFPM2 NM_012082.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.299

Genes affected

ZFPM2 (HGNC:16700): (zinc finger protein, FOG family member 2) The zinc finger protein encoded by this gene is a widely expressed member of the FOG family of transcription factors. The family members modulate the activity of GATA family proteins, which are important regulators of hematopoiesis and cardiogenesis in mammals. It has been demonstrated that the protein can both activate and down-regulate expression of GATA-target genes, suggesting different modulation in different promoter contexts. A related mRNA suggests an alternatively spliced product but this information is not yet fully supported by the sequence. [provided by RefSeq, Jul 2008]

ZFPM2-AS1 (HGNC:50698): (ZFPM2 antisense RNA 1)

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.72).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.283 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZFPM2	NM_012082.4	c.533-3567T>C		intron_variant		ENST00000407775.7	NP_036214.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZFPM2	ENST00000407775.7	c.533-3567T>C		intron_variant		1	NM_012082.4	ENSP00000384179.2

Frequencies

GnomAD3 genomes AF: 0.0823 AC: 12312 AN: 149670 Hom.: 1762 Cov.: 31

Gnomad AFR AF: 0.288

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0423

Gnomad ASJ AF: 0.0156

Gnomad EAS AF: 0.00309

Gnomad SAS AF: 0.0147

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0256

Gnomad NFE AF: 0.00200

Gnomad OTH AF: 0.0640

GnomAD4 exome Data not reliable, filtered out with message: AC0 AC: 0 AN: 0 Hom.: 0 Cov.: 0 AC XY: 0 AN XY: 0

GnomAD4 genome AF: 0.0824 AC: 12343 AN: 149786 Hom.: 1767 Cov.: 31 AF XY: 0.0796 AC XY: 5835 AN XY: 73272

Gnomad4 AFR AF: 0.288

Gnomad4 AMR AF: 0.0422

Gnomad4 ASJ AF: 0.0156

Gnomad4 EAS AF: 0.00290

Gnomad4 SAS AF: 0.0141

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00200

Gnomad4 OTH AF: 0.0642

Alfa AF: 0.0750 Hom.: 179

Bravo AF: 0.106

Asia WGS AF: 0.0420 AC: 147 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.72
CADD	Benign	6.4
DANN	Benign	0.77

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: rs7834726; hg19: chr8-106797379; COSMIC: COSV65874133;