rs2165646

Variant names:

• chr8-105642045-G-A
• rs2165646
• NM_012082.4:c.532+7688G>A

Variant summary

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

The NM_012082.4(ZFPM2):​c.532+7688G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.204 in 151,966 control chromosomes in the GnomAD database, including 3,159 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 0.20 (3159 hom., cov: 32)
• Consequence: ZFPM2 NM_012082.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.590
• 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-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=-0.56).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.241 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZFPM2	NM_012082.4	c.532+7688G>A		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.532+7688G>A		intron_variant	Intron 5 of 7	1	NM_012082.4	ENSP00000384179.2

Frequencies

GnomAD3 genomes AF: 0.204 AC: 30980 AN: 151850 Hom.: 3149 Cov.: 32

Gnomad AFR AF: 0.190

Gnomad AMI AF: 0.349

Gnomad AMR AF: 0.199

Gnomad ASJ AF: 0.220

Gnomad EAS AF: 0.144

Gnomad SAS AF: 0.254

Gnomad FIN AF: 0.245

Gnomad MID AF: 0.120

Gnomad NFE AF: 0.207

Gnomad OTH AF: 0.174

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

GnomAD4 genome AF: 0.204 AC: 31009 AN: 151966 Hom.: 3159 Cov.: 32 AF XY: 0.206 AC XY: 15311 AN XY: 74250

African (AFR) AF: 0.189 AC: 7855 AN: 41462

American (AMR) AF: 0.199 AC: 3039 AN: 15240

Ashkenazi Jewish (ASJ) AF: 0.220 AC: 764 AN: 3468

East Asian (EAS) AF: 0.144 AC: 744 AN: 5178

South Asian (SAS) AF: 0.253 AC: 1218 AN: 4818

European-Finnish (FIN) AF: 0.245 AC: 2590 AN: 10560

Middle Eastern (MID) AF: 0.126 AC: 37 AN: 294

European-Non Finnish (NFE) AF: 0.207 AC: 14067 AN: 67922

Other (OTH) AF: 0.178 AC: 377 AN: 2114

Alfa AF: 0.202 Hom.: 436

Bravo AF: 0.200

Asia WGS AF: 0.195 AC: 679 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.56
CADD	Benign	9.3
DANN	Benign	0.59
PhyloP100		0.59
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: rs2165646; hg19: chr8-106654273;