rs10505077

Positions:

• chr8-105623275-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The ENST00000407775.7(ZFPM2):​c.421-10971A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0105 in 152,234 control chromosomes in the GnomAD database, including 26 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 0.011 (26 hom., cov: 32)
• Consequence: ZFPM2 ENST00000407775.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.159

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BS1: Variant frequency is greater than expected in population amr. gnomad4 allele frequency = 0.0105 (1602/152234) while in subpopulation AMR AF= 0.0343 (524/15270). AF 95% confidence interval is 0.0319. There are 26 homozygotes in gnomad4. There are 932 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High AC in GnomAd4 at 1602 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZFPM2	NM_012082.4	c.421-10971A>G		intron_variant		ENST00000407775.7	NP_036214.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZFPM2	ENST00000407775.7	c.421-10971A>G		intron_variant		1	NM_012082.4	ENSP00000384179	P1

Frequencies

GnomAD3 genomes AF: 0.0105 AC: 1597 AN: 152116 Hom.: 24 Cov.: 32

Gnomad AFR AF: 0.00116

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0340

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.0237

Gnomad SAS AF: 0.00540

Gnomad FIN AF: 0.0407

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.00628

Gnomad OTH AF: 0.0106

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

GnomAD4 genome AF: 0.0105 AC: 1602 AN: 152234 Hom.: 26 Cov.: 32 AF XY: 0.0125 AC XY: 932 AN XY: 74424

Gnomad4 AFR AF: 0.00115

Gnomad4 AMR AF: 0.0343

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.0236

Gnomad4 SAS AF: 0.00561

Gnomad4 FIN AF: 0.0407

Gnomad4 NFE AF: 0.00628

Gnomad4 OTH AF: 0.00997

Alfa AF: 0.0103 Hom.: 3

Bravo AF: 0.0108

Asia WGS AF: 0.0140 AC: 50 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	2.7
DANN	Benign	0.82

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

Publications

LitVar

Other links and lift over

dbSNP: rs10505077; hg19: chr8-106635503;