dbSNP rs7834726: ZFPM2:c.533-3567T>C (chr8-105785151-T-C) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_012082.4(ZFPM2):c.533-3567T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0824 in 149,786 control chromosomes in the GnomAD database, including 1,767 homozygotes. There is a variant allele frequency bias in the population database for this variant (GnomAd4), which may indicate mosaicism or somatic mutations in the reference population data. 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 0.082 ( 1767 hom., cov: 31)

Failed GnomAD Quality Control

Consequence

ZFPM2
NM_012082.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.299

Publications

1 publications found

Variant links:

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 links:

ZFPM2-AS1 (HGNC:50698): (ZFPM2 antisense RNA 1)

ZFPM2-AS1 links:

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -4 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.72).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_012082.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
ZFPM2	NM_012082.4	MANE Select	c.533-3567T>C	intron	N/A	NP_036214.2
ZFPM2-AS1	NR_125796.1		n.667A>G	non_coding_transcript_exon	Exon 6 of 8
ZFPM2	NM_001362836.2		c.374-3567T>C	intron	N/A	NP_001349765.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
ZFPM2	ENST00000407775.7	TSL:1 MANE Select	c.533-3567T>C	intron	N/A	ENSP00000384179.2
ZFPM2	ENST00000511341.6	TSL:1	n.1273-3567T>C	intron	N/A
ZFPM2-AS1	ENST00000518932.5	TSL:2	n.553A>G	non_coding_transcript_exon	Exon 5 of 5

Frequencies

GnomAD3 genomes

AF:

0.0823

AC:

12312

AN:

149670

Hom.:

1762

Cov.:

show subpopulations

Gnomad AFR

AF:

0.288

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0423

Gnomad ASJ

AF:

0.0156

Gnomad EAS

AF:

0.00309

Gnomad SAS

AF:

0.0147

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.0256

Gnomad NFE

AF:

0.00200

Gnomad OTH

AF:

0.0640

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AC:

AN:

Hom.:

Cov.:

AC XY:

AN XY:

African (AFR)

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AC:

AN:

Other (OTH)

AC:

AN:

GnomAD4 genome

AF:

0.0824

AC:

12343

AN:

149786

Hom.:

1767

Cov.:

AF XY:

0.0796

AC XY:

5835

AN XY:

73272

show subpopulations

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.

African (AFR)

AF:

0.288

AC:

11288

AN:

39258

American (AMR)

AF:

0.0422

AC:

640

AN:

15164

Ashkenazi Jewish (ASJ)

AF:

0.0156

AC:

AN:

3458

East Asian (EAS)

AF:

0.00290

AC:

AN:

5168

South Asian (SAS)

AF:

0.0141

AC:

AN:

4812

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10614

Middle Eastern (MID)

AF:

0.0276

AC:

AN:

290

European-Non Finnish (NFE)

AF:

0.00200

AC:

136

AN:

68024

Other (OTH)

AF:

0.0642

AC:

134

AN:

2086

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.367

Heterozygous variant carriers

391

781

1172

1562

1953

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

110

220

330

440

550

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0843

Hom.:

213

Bravo

AF:

0.106

Asia WGS

AF:

0.0420

AC:

147

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.72

CADD

Benign

6.4

(source)

DANN

Benign

0.77

PhyloP100

0.30

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over