ENST00000518180.1:n.197-44252C>T

Variant names:

• chr8-104947372-C-T
• rs284492
• ENST00000518180.1:n.197-44252C>T

Variant summary

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

The ENST00000518180.1(ZFPM2):​n.197-44252C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.444 in 151,690 control chromosomes in the GnomAD database, including 16,549 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 (16549 hom., cov: 32)
• Consequence: ZFPM2 ENST00000518180.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -4.41
• 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

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.647 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000518180.1. 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	ENST00000518180.1	TSL:4	n.197-44252C>T		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.444 AC: 67235 AN: 151570 Hom.: 16500 Cov.: 32

Gnomad AFR AF: 0.653

Gnomad AMI AF: 0.323

Gnomad AMR AF: 0.399

Gnomad ASJ AF: 0.356

Gnomad EAS AF: 0.405

Gnomad SAS AF: 0.279

Gnomad FIN AF: 0.538

Gnomad MID AF: 0.354

Gnomad NFE AF: 0.334

Gnomad OTH AF: 0.400

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

GnomAD4 genome AF: 0.444 AC: 67347 AN: 151690 Hom.: 16549 Cov.: 32 AF XY: 0.449 AC XY: 33273 AN XY: 74102

African (AFR) AF: 0.654 AC: 27079 AN: 41410

American (AMR) AF: 0.399 AC: 6075 AN: 15226

Ashkenazi Jewish (ASJ) AF: 0.356 AC: 1229 AN: 3456

East Asian (EAS) AF: 0.405 AC: 2062 AN: 5094

South Asian (SAS) AF: 0.278 AC: 1337 AN: 4816

European-Finnish (FIN) AF: 0.538 AC: 5684 AN: 10556

Middle Eastern (MID) AF: 0.361 AC: 106 AN: 294

European-Non Finnish (NFE) AF: 0.334 AC: 22633 AN: 67822

Other (OTH) AF: 0.403 AC: 848 AN: 2106

Alfa AF: 0.417 Hom.: 1815

Bravo AF: 0.442

Asia WGS AF: 0.396 AC: 1378 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.094
DANN	Benign	0.63
PhyloP100		-4.4

Splicing

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

Other links and lift over

dbSNP: rs284492; hg19: chr8-105959600;