rs16872085

Variant names:

• chr8-104945312-A-G
• rs16872085
• ENST00000518180.1:n.197-46312A>G

Variant summary

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

The ENST00000518180.1(ZFPM2):​n.197-46312A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0788 in 152,064 control chromosomes in the GnomAD database, including 589 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 0.079 (589 hom., cov: 32)
• Consequence: ZFPM2 ENST00000518180.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.469
• Publications: 7 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=-0.83).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.232 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.197-46312A>G		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.0789 AC: 11989 AN: 151946 Hom.: 589 Cov.: 32

Gnomad AFR AF: 0.0541

Gnomad AMI AF: 0.0121

Gnomad AMR AF: 0.0688

Gnomad ASJ AF: 0.154

Gnomad EAS AF: 0.243

Gnomad SAS AF: 0.103

Gnomad FIN AF: 0.0680

Gnomad MID AF: 0.0886

Gnomad NFE AF: 0.0809

Gnomad OTH AF: 0.0799

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

GnomAD4 genome AF: 0.0788 AC: 11982 AN: 152064 Hom.: 589 Cov.: 32 AF XY: 0.0794 AC XY: 5903 AN XY: 74320

African (AFR) AF: 0.0539 AC: 2239 AN: 41532

American (AMR) AF: 0.0687 AC: 1048 AN: 15254

Ashkenazi Jewish (ASJ) AF: 0.154 AC: 533 AN: 3466

East Asian (EAS) AF: 0.243 AC: 1247 AN: 5128

South Asian (SAS) AF: 0.102 AC: 494 AN: 4822

European-Finnish (FIN) AF: 0.0680 AC: 721 AN: 10610

Middle Eastern (MID) AF: 0.0850 AC: 25 AN: 294

European-Non Finnish (NFE) AF: 0.0809 AC: 5495 AN: 67934

Other (OTH) AF: 0.0800 AC: 169 AN: 2112

Alfa AF: 0.0861 Hom.: 1743

Bravo AF: 0.0799

Asia WGS AF: 0.138 AC: 478 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	5.3
DANN	Benign	0.70
PhyloP100		0.47

Splicing

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

Other links and lift over

dbSNP: rs16872085; hg19: chr8-105957540;