8-104945792-A-G

Variant names:

• chr8-104945792-A-G
• rs284489
• ENST00000518180.1:n.197-45832A>G

Variant summary

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

The ENST00000518180.1(ZFPM2):​n.197-45832A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.442 in 151,830 control chromosomes in the GnomAD database, including 16,133 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 0.44 (16133 hom., cov: 32)
• Consequence: ZFPM2 ENST00000518180.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.00800
• Publications: 24 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=-0.78).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.619 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	ENST00000518180.1	n.197-45832A>G		intron_variant	Intron 2 of 4	4

Frequencies

GnomAD3 genomes AF: 0.442 AC: 66984 AN: 151712 Hom.: 16106 Cov.: 32

Gnomad AFR AF: 0.625

Gnomad AMI AF: 0.325

Gnomad AMR AF: 0.399

Gnomad ASJ AF: 0.363

Gnomad EAS AF: 0.414

Gnomad SAS AF: 0.323

Gnomad FIN AF: 0.548

Gnomad MID AF: 0.369

Gnomad NFE AF: 0.341

Gnomad OTH AF: 0.397

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

GnomAD4 genome AF: 0.442 AC: 67070 AN: 151830 Hom.: 16133 Cov.: 32 AF XY: 0.448 AC XY: 33212 AN XY: 74186

African (AFR) AF: 0.625 AC: 25900 AN: 41428

American (AMR) AF: 0.399 AC: 6085 AN: 15246

Ashkenazi Jewish (ASJ) AF: 0.363 AC: 1261 AN: 3470

East Asian (EAS) AF: 0.414 AC: 2121 AN: 5122

South Asian (SAS) AF: 0.322 AC: 1551 AN: 4824

European-Finnish (FIN) AF: 0.548 AC: 5793 AN: 10570

Middle Eastern (MID) AF: 0.370 AC: 108 AN: 292

European-Non Finnish (NFE) AF: 0.341 AC: 23111 AN: 67856

Other (OTH) AF: 0.400 AC: 844 AN: 2110

Alfa AF: 0.369 Hom.: 49382

Bravo AF: 0.437

Asia WGS AF: 0.413 AC: 1435 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	6.6
DANN	Benign	0.91
PhyloP100		0.0080

Splicing

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

Other links and lift over

dbSNP: rs284489; hg19: chr8-105958020;