8-105561691-C-T

Variant names:

• chr8-105561691-C-T
• rs12216772
• NM_012082.4:c.420+210C>T

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_012082.4(ZFPM2):​c.420+210C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.422 in 151,932 control chromosomes in the GnomAD database, including 13,508 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.42 (13508 hom., cov: 32)
• Consequence: ZFPM2 NM_012082.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.70
• Publications: 2 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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.47).
• BP6: Variant 8-105561691-C-T is Benign according to our data. Variant chr8-105561691-C-T is described in ClinVar as [Benign]. Clinvar id is 1227492.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.467 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZFPM2	NM_012082.4	c.420+210C>T		intron_variant	Intron 4 of 7	ENST00000407775.7	NP_036214.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZFPM2	ENST00000407775.7	c.420+210C>T		intron_variant	Intron 4 of 7	1	NM_012082.4	ENSP00000384179.2

Frequencies

GnomAD3 genomes AF: 0.422 AC: 64084 AN: 151816 Hom.: 13510 Cov.: 32

Gnomad AFR AF: 0.418

Gnomad AMI AF: 0.286

Gnomad AMR AF: 0.383

Gnomad ASJ AF: 0.481

Gnomad EAS AF: 0.446

Gnomad SAS AF: 0.484

Gnomad FIN AF: 0.343

Gnomad MID AF: 0.456

Gnomad NFE AF: 0.438

Gnomad OTH AF: 0.439

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

GnomAD4 genome AF: 0.422 AC: 64096 AN: 151932 Hom.: 13508 Cov.: 32 AF XY: 0.416 AC XY: 30891 AN XY: 74248

African (AFR) AF: 0.418 AC: 17307 AN: 41418

American (AMR) AF: 0.382 AC: 5835 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.481 AC: 1669 AN: 3472

East Asian (EAS) AF: 0.446 AC: 2298 AN: 5152

South Asian (SAS) AF: 0.483 AC: 2327 AN: 4816

European-Finnish (FIN) AF: 0.343 AC: 3615 AN: 10554

Middle Eastern (MID) AF: 0.439 AC: 129 AN: 294

European-Non Finnish (NFE) AF: 0.438 AC: 29733 AN: 67940

Other (OTH) AF: 0.438 AC: 923 AN: 2106

Alfa AF: 0.430 Hom.: 4914

Bravo AF: 0.419

Asia WGS AF: 0.482 AC: 1673 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Nov 13, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.47
CADD	Benign	14
DANN	Benign	0.44
PhyloP100		1.7
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: rs12216772; hg19: chr8-106573919;