chr22-49894697-A-G

Variant names:

• chr22-49894697-A-G
• rs6520141
• XM_017028936.2:c.1238+9482T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000850560.1(ZBED4):​n.261-453A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.257 in 152,248 control chromosomes in the GnomAD database, including 9,994 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 0.26 (9994 hom., cov: 33)
• Consequence: ZBED4 ENST00000850560.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.246
• Publications: 9 publications found

Genes affected

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]

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]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.657 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000850560.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
There are no transcript annotations for this variant.

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZBED4	ENST00000850560.1		n.261-453A>G		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.257 AC: 39082 AN: 152130 Hom.: 9960 Cov.: 33

Gnomad AFR AF: 0.664

Gnomad AMI AF: 0.292

Gnomad AMR AF: 0.135

Gnomad ASJ AF: 0.154

Gnomad EAS AF: 0.102

Gnomad SAS AF: 0.223

Gnomad FIN AF: 0.0447

Gnomad MID AF: 0.212

Gnomad NFE AF: 0.0902

Gnomad OTH AF: 0.221

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

GnomAD4 genome AF: 0.257 AC: 39166 AN: 152248 Hom.: 9994 Cov.: 33 AF XY: 0.252 AC XY: 18762 AN XY: 74450

African (AFR) AF: 0.664 AC: 27564 AN: 41514

American (AMR) AF: 0.135 AC: 2060 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.154 AC: 536 AN: 3472

East Asian (EAS) AF: 0.103 AC: 533 AN: 5180

South Asian (SAS) AF: 0.222 AC: 1071 AN: 4826

European-Finnish (FIN) AF: 0.0447 AC: 475 AN: 10622

Middle Eastern (MID) AF: 0.194 AC: 57 AN: 294

European-Non Finnish (NFE) AF: 0.0902 AC: 6135 AN: 68012

Other (OTH) AF: 0.222 AC: 470 AN: 2114

Alfa AF: 0.228 Hom.: 1933

Bravo AF: 0.278

Asia WGS AF: 0.201 AC: 697 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	3.9
DANN	Benign	0.71
PhyloP100		-0.25

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs6520141;

hg19: chr22-50288345;