8-105754490-A-G

Variant names:

• chr8-105754490-A-G
• rs16873632
• NM_012082.4:c.533-34228A>G

Variant summary

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

The NM_012082.4(ZFPM2):​c.533-34228A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.104 in 152,072 control chromosomes in the GnomAD database, including 1,050 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 0.10 (1050 hom., cov: 32)
• Consequence: ZFPM2 NM_012082.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0790
• Publications: 1 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-AS1 (HGNC:50698): (ZFPM2 antisense RNA 1)

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.321 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZFPM2	NM_012082.4	c.533-34228A>G		intron_variant	Intron 5 of 7	ENST00000407775.7	NP_036214.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZFPM2	ENST00000407775.7	c.533-34228A>G		intron_variant	Intron 5 of 7	1	NM_012082.4	ENSP00000384179.2

Frequencies

GnomAD3 genomes AF: 0.104 AC: 15764 AN: 151954 Hom.: 1042 Cov.: 32

Gnomad AFR AF: 0.0959

Gnomad AMI AF: 0.0175

Gnomad AMR AF: 0.113

Gnomad ASJ AF: 0.0890

Gnomad EAS AF: 0.335

Gnomad SAS AF: 0.0933

Gnomad FIN AF: 0.0668

Gnomad MID AF: 0.0728

Gnomad NFE AF: 0.0979

Gnomad OTH AF: 0.0962

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

GnomAD4 genome AF: 0.104 AC: 15797 AN: 152072 Hom.: 1050 Cov.: 32 AF XY: 0.105 AC XY: 7775 AN XY: 74334

African (AFR) AF: 0.0962 AC: 3996 AN: 41524

American (AMR) AF: 0.112 AC: 1714 AN: 15248

Ashkenazi Jewish (ASJ) AF: 0.0890 AC: 309 AN: 3470

East Asian (EAS) AF: 0.335 AC: 1710 AN: 5110

South Asian (SAS) AF: 0.0924 AC: 445 AN: 4818

European-Finnish (FIN) AF: 0.0668 AC: 709 AN: 10610

Middle Eastern (MID) AF: 0.0748 AC: 22 AN: 294

European-Non Finnish (NFE) AF: 0.0979 AC: 6655 AN: 67974

Other (OTH) AF: 0.105 AC: 221 AN: 2112

Alfa AF: 0.101 Hom.: 167

Bravo AF: 0.107

Asia WGS AF: 0.250 AC: 866 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	13
DANN	Benign	0.69
PhyloP100		0.079
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs16873632; hg19: chr8-106766718; COSMIC: COSV107514633;