rs6993770

chr8-105569300-A-T

Variant summary

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

The NM_012082.4(ZFPM2):c.420+7819A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.314 in 152,040 control chromosomes in the GnomAD database, including 7,709 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 0.31 (7709 hom., cov: 32)
• Consequence: ZFPM2 NM_012082.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.424

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=-0.82).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.39 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ZFPM2	NM_012082.4	c.420+7819A>T		intron_variant		ENST00000407775.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ZFPM2	ENST00000407775.7	c.420+7819A>T		intron_variant		1	NM_012082.4	P1

Frequencies

GnomAD3 genomes AF: 0.314 AC: 47721 AN: 151920 Hom.: 7707 Cov.: 32

Gnomad AFR AF: 0.379

Gnomad AMI AF: 0.157

Gnomad AMR AF: 0.303

Gnomad ASJ AF: 0.357

Gnomad EAS AF: 0.405

Gnomad SAS AF: 0.350

Gnomad FIN AF: 0.218

Gnomad MID AF: 0.323

Gnomad NFE AF: 0.282

Gnomad OTH AF: 0.343

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

GnomAD4 genome AF: 0.314 AC: 47742 AN: 152040 Hom.: 7709 Cov.: 32 AF XY: 0.311 AC XY: 23106 AN XY: 74296

Gnomad4 AFR AF: 0.379

Gnomad4 AMR AF: 0.302

Gnomad4 ASJ AF: 0.357

Gnomad4 EAS AF: 0.405

Gnomad4 SAS AF: 0.349

Gnomad4 FIN AF: 0.218

Gnomad4 NFE AF: 0.282

Gnomad4 OTH AF: 0.344

Alfa AF: 0.296 Hom.: 852

Bravo AF: 0.322

Asia WGS AF: 0.396 AC: 1376 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
Cadd	Benign	0.45
Dann	Benign	0.54

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: rs6993770; hg19: chr8-106581528;