rs6993770

Variant names:

• chr8-105569300-A-T
• rs6993770
• NM_012082.4:c.420+7819A>T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 50 publications found

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

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
ZFPM2	NM_012082.4	c.420+7819A>T		intron_variant	Intron 4 of 7	ENST00000407775.7	NP_036214.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZFPM2	ENST00000407775.7	c.420+7819A>T		intron_variant	Intron 4 of 7	1	NM_012082.4	ENSP00000384179.2

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

African (AFR) AF: 0.379 AC: 15694 AN: 41462

American (AMR) AF: 0.302 AC: 4611 AN: 15256

Ashkenazi Jewish (ASJ) AF: 0.357 AC: 1241 AN: 3472

East Asian (EAS) AF: 0.405 AC: 2086 AN: 5156

South Asian (SAS) AF: 0.349 AC: 1681 AN: 4816

European-Finnish (FIN) AF: 0.218 AC: 2307 AN: 10576

Middle Eastern (MID) AF: 0.303 AC: 89 AN: 294

European-Non Finnish (NFE) AF: 0.282 AC: 19163 AN: 67984

Other (OTH) AF: 0.344 AC: 727 AN: 2114

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
PhyloP100		-0.42
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: rs6993770; hg19: chr8-106581528;