chr8-104698507-G-A

Variant names:

• chr8-104698507-G-A
• rs7845583
• ENST00000521923.5:n.37-16339G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000521923.5(ZFPM2):​n.37-16339G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.662 in 151,958 control chromosomes in the GnomAD database, including 33,726 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 0.66 (33726 hom., cov: 32)
• Consequence: ZFPM2 ENST00000521923.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.302
• Publications: 2 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 Gene-Disease associations (from GenCC):

• 46,XY sex reversal 9

  Inheritance: AD Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)
• diaphragmatic hernia 3

  Inheritance: AD Classification: STRONG, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), G2P
• tetralogy of fallot

  Inheritance: Unknown, AD Classification: STRONG, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics
• 46,XY partial gonadal dysgenesis

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ENSG00000283157 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.709 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000521923.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
There are no transcript annotations for this variant.

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZFPM2	ENST00000521923.5	TSL:3	n.37-16339G>A		intron	N/A
	ENSG00000283157	ENST00000849119.1		n.82-2163C>T		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.662 AC: 100550 AN: 151840 Hom.: 33692 Cov.: 32

Gnomad AFR AF: 0.631

Gnomad AMI AF: 0.765

Gnomad AMR AF: 0.543

Gnomad ASJ AF: 0.641

Gnomad EAS AF: 0.505

Gnomad SAS AF: 0.608

Gnomad FIN AF: 0.739

Gnomad MID AF: 0.522

Gnomad NFE AF: 0.714

Gnomad OTH AF: 0.613

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

GnomAD4 genome AF: 0.662 AC: 100633 AN: 151958 Hom.: 33726 Cov.: 32 AF XY: 0.659 AC XY: 48962 AN XY: 74250

African (AFR) AF: 0.631 AC: 26136 AN: 41422

American (AMR) AF: 0.543 AC: 8288 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.641 AC: 2223 AN: 3470

East Asian (EAS) AF: 0.506 AC: 2617 AN: 5170

South Asian (SAS) AF: 0.608 AC: 2926 AN: 4816

European-Finnish (FIN) AF: 0.739 AC: 7795 AN: 10544

Middle Eastern (MID) AF: 0.531 AC: 156 AN: 294

European-Non Finnish (NFE) AF: 0.714 AC: 48510 AN: 67954

Other (OTH) AF: 0.609 AC: 1284 AN: 2110

Alfa AF: 0.672 Hom.: 5298

Bravo AF: 0.641

Asia WGS AF: 0.568 AC: 1975 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	1.0
DANN	Benign	0.64
PhyloP100		-0.30

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs7845583; hg19: chr8-105710735;