chr22-49884920-A-G

Position:

• chr22-49884920-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000216268.6(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 same amino acid change has been previously reported as Likely benignin UniProt.

• Frequency:
  • Genomes: 𝑓 0.65 (36656 hom., cov: 34)
  • Exomes 𝑓: 0.79 (455008 hom.)
• Consequence: ZBED4 ENST00000216268.6 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.40

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]

ALG12 (HGNC:):

ACMG classification

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/exons	MANE	Protein	UniProt
ZBED4	NM_014838.3	c.1258A>G	p.Ile420Val	missense_variant	2/2	ENST00000216268.6	NP_055653.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZBED4	ENST00000216268.6	c.1258A>G	p.Ile420Val	missense_variant	2/2	1	NM_014838.3	ENSP00000216268	P1

Frequencies

GnomAD3 genomes AF: 0.654 AC: 99413 AN: 152108 Hom.: 36655 Cov.: 34

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

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.: 89 AF XY: 0.782 AC XY: 564471 AN XY: 722026

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.: 34 AF XY: 0.659 AC XY: 49038 AN XY: 74420

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	T
BayesDel_noAF	Benign	-0.76
CADD	Benign	0.10
DANN	Benign	0.24
DEOGEN2	Benign	0.021	T
Eigen	Benign	-1.4
Eigen_PC	Benign	-1.4
FATHMM_MKL	Benign	0.043	N
LIST_S2	Benign	0.12	T
MetaRNN	Benign	9.5e-7	T
MetaSVM	Benign	-0.93	T
MutationAssessor	Benign	-0.095	N
MutationTaster	Benign	1.0	P
PrimateAI	Benign	0.38	T
PROVEAN	Benign	0.070	N
REVEL	Benign	0.029
Sift	Benign	1.0	T
Sift4G	Benign	0.62	T
Polyphen		0.0	B
Vest4		0.0090
MPC		0.35
ClinPred		0.0065	T
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

Other links and lift over

dbSNP: rs910799; hg19: chr22-50278568; COSMIC: COSV53467145;