ENST00000521923.5:n.37-26394A>G

Variant names:

• chr8-104688452-A-G
• rs4734806
• ENST00000521923.5:n.37-26394A>G

Variant summary

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

The ENST00000521923.5(ZFPM2):​n.37-26394A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.146 in 152,196 control chromosomes in the GnomAD database, including 1,850 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 0.15 (1850 hom., cov: 32)
• Consequence: ZFPM2 ENST00000521923.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.90
• Publications: 4 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

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.186 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZFPM2	ENST00000521923.5	n.37-26394A>G		intron_variant	Intron 1 of 4	3

Frequencies

GnomAD3 genomes AF: 0.146 AC: 22190 AN: 152078 Hom.: 1847 Cov.: 32

Gnomad AFR AF: 0.0953

Gnomad AMI AF: 0.224

Gnomad AMR AF: 0.137

Gnomad ASJ AF: 0.146

Gnomad EAS AF: 0.0141

Gnomad SAS AF: 0.195

Gnomad FIN AF: 0.210

Gnomad MID AF: 0.174

Gnomad NFE AF: 0.174

Gnomad OTH AF: 0.149

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

GnomAD4 genome AF: 0.146 AC: 22213 AN: 152196 Hom.: 1850 Cov.: 32 AF XY: 0.148 AC XY: 11038 AN XY: 74396

African (AFR) AF: 0.0954 AC: 3963 AN: 41554

American (AMR) AF: 0.137 AC: 2095 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.146 AC: 506 AN: 3470

East Asian (EAS) AF: 0.0139 AC: 72 AN: 5168

South Asian (SAS) AF: 0.197 AC: 947 AN: 4812

European-Finnish (FIN) AF: 0.210 AC: 2226 AN: 10588

Middle Eastern (MID) AF: 0.180 AC: 53 AN: 294

European-Non Finnish (NFE) AF: 0.174 AC: 11832 AN: 68002

Other (OTH) AF: 0.149 AC: 315 AN: 2114

Alfa AF: 0.171 Hom.: 1191

Bravo AF: 0.138

Asia WGS AF: 0.131 AC: 456 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	0.13
DANN	Benign	0.56
PhyloP100		-1.9

Splicing

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

Other links and lift over

dbSNP: rs4734806; hg19: chr8-105700680;