8-105754490-A-G

Position:

• chr8-105754490-A-G

Variant summary

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

The NM_012082.4(ZFPM2):​c.533-34228A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.104 in 152,072 control chromosomes in the GnomAD database, including 1,050 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 0.10 (1050 hom., cov: 32)
• Consequence: ZFPM2 NM_012082.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0790

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=-0.84).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.321 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ZFPM2	NM_012082.4	c.533-34228A>G		intron_variant		ENST00000407775.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ZFPM2	ENST00000407775.7	c.533-34228A>G		intron_variant		1	NM_012082.4	P1

Frequencies

GnomAD3 genomes AF: 0.104 AC: 15764 AN: 151954 Hom.: 1042 Cov.: 32

Gnomad AFR AF: 0.0959

Gnomad AMI AF: 0.0175

Gnomad AMR AF: 0.113

Gnomad ASJ AF: 0.0890

Gnomad EAS AF: 0.335

Gnomad SAS AF: 0.0933

Gnomad FIN AF: 0.0668

Gnomad MID AF: 0.0728

Gnomad NFE AF: 0.0979

Gnomad OTH AF: 0.0962

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

GnomAD4 genome AF: 0.104 AC: 15797 AN: 152072 Hom.: 1050 Cov.: 32 AF XY: 0.105 AC XY: 7775 AN XY: 74334

Gnomad4 AFR AF: 0.0962

Gnomad4 AMR AF: 0.112

Gnomad4 ASJ AF: 0.0890

Gnomad4 EAS AF: 0.335

Gnomad4 SAS AF: 0.0924

Gnomad4 FIN AF: 0.0668

Gnomad4 NFE AF: 0.0979

Gnomad4 OTH AF: 0.105

Alfa AF: 0.101 Hom.: 167

Bravo AF: 0.107

Asia WGS AF: 0.250 AC: 866 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	13
DANN	Benign	0.69

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: rs16873632; hg19: chr8-106766718;