dbSNP rs910799: ZBED4:p.Ile420Val (chr22-49884920-A-G) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_014838.3(ZBED4):c.1258A>G(p.Ile420Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.773 in 1,605,264 control chromosomes in the GnomAD database, including 491,664 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Likely benign in UniProt.

Frequency

Genomes: 𝑓 0.65 ( 36656 hom., cov: 34)

Exomes 𝑓: 0.79 ( 455008 hom. )

Consequence

ZBED4
NM_014838.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.40

Variant links:

Genes affected

ZBED4 (HGNC:20721): (zinc finger BED-type containing 4) Enables identical protein binding activity. Predicted to be involved in positive regulation of transcription by RNA polymerase II. Located in cytoplasm and nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

ZBED4 links:

ALG12 (HGNC:19358): (ALG12 alpha-1,6-mannosyltransferase) This gene encodes a member of the glycosyltransferase 22 family. The encoded protein catalyzes the addition of the eighth mannose residue in an alpha-1,6 linkage onto the dolichol-PP-oligosaccharide precursor (dolichol-PP-Man(7)GlcNAc(2)) required for protein glycosylation. Mutations in this gene have been associated with congenital disorder of glycosylation type Ig (CDG-Ig)characterized by abnormal N-glycosylation. [provided by RefSeq, Jul 2008]

ALG12 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=9.5252267E-7).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.835 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZBED4	NM_014838.3 link	c.1258A>G	p.Ile420Val	missense_variant	Exon 2 of 2	ENST00000216268.6	NP_055653.2	O75132

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZBED4	ENST00000216268.6 link	c.1258A>G	p.Ile420Val	missense_variant	Exon 2 of 2	1	NM_014838.3	ENSP00000216268.4		O75132

Frequencies

GnomAD3 genomes

AF:

0.654

AC:

99413

AN:

152108

Hom.:

36655

Cov.:

show subpopulations

Gnomad AFR

AF:

0.277

Gnomad AMI

AF:

0.533

Gnomad AMR

AF:

0.784

Gnomad ASJ

AF:

0.754

Gnomad EAS

AF:

0.856

Gnomad SAS

AF:

0.656

Gnomad FIN

AF:

0.842

Gnomad MID

AF:

0.707

Gnomad NFE

AF:

0.803

Gnomad OTH

AF:

0.703

GnomAD3 exomes

AF:

0.761

AC:

186306

AN:

244900

Hom.:

73621

AF XY:

0.761

AC XY:

100727

AN XY:

132396

show subpopulations

Gnomad AFR exome

AF:

0.264

Gnomad AMR exome

AF:

0.854

Gnomad ASJ exome

AF:

0.745

Gnomad EAS exome

AF:

0.868

Gnomad SAS exome

AF:

0.637

Gnomad FIN exome

AF:

0.846

Gnomad NFE exome

AF:

0.804

Gnomad OTH exome

AF:

0.780

GnomAD4 exome

AF:

0.786

AC:

1141378

AN:

1453038

Hom.:

455008

Cov.:

AF XY:

0.782

AC XY:

564471

AN XY:

722026

show subpopulations

Gnomad4 AFR exome

AF:

0.253

Gnomad4 AMR exome

AF:

0.846

Gnomad4 ASJ exome

AF:

0.755

Gnomad4 EAS exome

AF:

0.863

Gnomad4 SAS exome

AF:

0.641

Gnomad4 FIN exome

AF:

0.842

Gnomad4 NFE exome

AF:

0.807

Gnomad4 OTH exome

AF:

0.760

GnomAD4 genome

AF:

0.653

AC:

99415

AN:

152226

Hom.:

36656

Cov.:

AF XY:

0.659

AC XY:

49038

AN XY:

74420

show subpopulations

Gnomad4 AFR

AF:

0.277

Gnomad4 AMR

AF:

0.785

Gnomad4 ASJ

AF:

0.754

Gnomad4 EAS

AF:

0.856

Gnomad4 SAS

AF:

0.657

Gnomad4 FIN

AF:

0.842

Gnomad4 NFE

AF:

0.803

Gnomad4 OTH

AF:

0.699

Alfa

AF:

0.786

Hom.:

104761

Bravo

AF:

0.639

TwinsUK

AF:

0.806

AC:

2987

ALSPAC

AF:

0.807

AC:

3112

ESP6500AA

AF:

0.293

AC:

1292

ESP6500EA

AF:

0.797

AC:

6858

ExAC

AF:

0.748

AC:

90722

Asia WGS

AF:

0.701

AC:

2438

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.057

BayesDel_addAF

Benign

-0.79

BayesDel_noAF

Benign

-0.76

CADD

Benign

0.10

DANN

Benign

0.24

DEOGEN2

Benign

0.021

Eigen

Benign

-1.4

Eigen_PC

Benign

-1.4

FATHMM_MKL

Benign

0.043

LIST_S2

Benign

0.12

MetaRNN

Benign

9.5e-7

MetaSVM

Benign

-0.93

MutationAssessor

Benign

-0.095

PrimateAI

Benign

0.38

PROVEAN

Benign

0.070

REVEL

Benign

0.029

Sift

Benign

1.0

Sift4G

Benign

0.62

Polyphen

0.0

Vest4

0.0090

MPC

0.35

ClinPred

0.0065

GERP RS

0.48

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.019

gMVP

0.12

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over