rs1350724

Variant names:

• chr8-105065469-C-T
• rs1350724
• ENST00000518180.1:n.242+73800C>T

Variant summary

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

The ENST00000518180.1(ZFPM2):​n.242+73800C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0799 in 151,990 control chromosomes in the GnomAD database, including 1,470 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 0.080 (1470 hom., cov: 31)
• Consequence: ZFPM2 ENST00000518180.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.160
• Publications: 0 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=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.258 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.242+73800C>T		intron_variant	Intron 3 of 4	4

Frequencies

GnomAD3 genomes AF: 0.0798 AC: 12118 AN: 151872 Hom.: 1465 Cov.: 31

Gnomad AFR AF: 0.262

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0407

Gnomad ASJ AF: 0.0150

Gnomad EAS AF: 0.00193

Gnomad SAS AF: 0.00830

Gnomad FIN AF: 0.00132

Gnomad MID AF: 0.0475

Gnomad NFE AF: 0.00591

Gnomad OTH AF: 0.0645

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

GnomAD4 genome AF: 0.0799 AC: 12146 AN: 151990 Hom.: 1470 Cov.: 31 AF XY: 0.0771 AC XY: 5729 AN XY: 74286

African (AFR) AF: 0.262 AC: 10861 AN: 41384

American (AMR) AF: 0.0406 AC: 619 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.0150 AC: 52 AN: 3472

East Asian (EAS) AF: 0.00194 AC: 10 AN: 5160

South Asian (SAS) AF: 0.00768 AC: 37 AN: 4818

European-Finnish (FIN) AF: 0.00132 AC: 14 AN: 10586

Middle Eastern (MID) AF: 0.0544 AC: 16 AN: 294

European-Non Finnish (NFE) AF: 0.00591 AC: 402 AN: 67988

Other (OTH) AF: 0.0639 AC: 135 AN: 2114

Alfa AF: 0.113 Hom.: 816

Bravo AF: 0.0906

Asia WGS AF: 0.0310 AC: 109 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	1.1
DANN	Benign	0.22
PhyloP100		-0.16

Splicing

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

Other links and lift over

dbSNP: rs1350724; hg19: chr8-106077697;