chr11-10853276-C-T

Variant names:

• chr11-10853276-C-T
• rs867818881
• NM_001143667.2:c.1670G>A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001143667.2(ZBED5):​c.1670G>A​(p.Arg557His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000029 in 1,551,420 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R557C) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.000039 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000028 (0 hom.)
• Consequence: ZBED5 NM_001143667.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.104
• Publications: 1 publications found

Genes affected

ZBED5 (HGNC:30803): (zinc finger BED-type containing 5) This gene is unusual in that its coding sequence is mostly derived from Charlie-like DNA transposon; however, it does not appear to be an active DNA transposon as it is not flanked by terminal inverted repeats. The encoded protein is conserved among the mammalian Laurasiatheria branch. Multiple alternatively spliced variants, encoding the same protein, have been identified. [provided by RefSeq, Jan 2009]

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.03307447).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001143667.2. 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
	ZBED5	NM_001143667.2	MANE Select	c.1670G>A	p.Arg557His	missense	Exon 3 of 3	NP_001137139.1	Q49AG3
	ZBED5	NM_021211.4		c.1670G>A	p.Arg557His	missense	Exon 3 of 3	NP_067034.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZBED5	ENST00000413761.7	TSL:1 MANE Select	c.1670G>A	p.Arg557His	missense	Exon 3 of 3	ENSP00000415939.2	Q49AG3
	ZBED5	ENST00000432999.6	TSL:1	c.1670G>A	p.Arg557His	missense	Exon 3 of 3	ENSP00000398106.2	Q49AG3
	ZBED5	ENST00000876894.1		c.1670G>A	p.Arg557His	missense	Exon 2 of 2	ENSP00000546953.1

Frequencies

GnomAD3 genomes AF: 0.0000394 AC: 6 AN: 152122 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000724

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000192

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000294

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000392 AC: 6 AN: 153202 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000265

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000174

Gnomad OTH exome AF: 0.000228

GnomAD4 exome AF: 0.0000279 AC: 39 AN: 1399298 Hom.: 0 Cov.: 31 AF XY: 0.0000188 AC XY: 13 AN XY: 690150

African (AFR) AF: 0.0000317 AC: 1 AN: 31590

American (AMR) AF: 0.00 AC: 0 AN: 35696

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25174

East Asian (EAS) AF: 0.000168 AC: 6 AN: 35734

South Asian (SAS) AF: 0.0000126 AC: 1 AN: 79228

European-Finnish (FIN) AF: 0.0000203 AC: 1 AN: 49274

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5698

European-Non Finnish (NFE) AF: 0.0000269 AC: 29 AN: 1078914

Other (OTH) AF: 0.0000172 AC: 1 AN: 57990

GnomAD4 genome AF: 0.0000394 AC: 6 AN: 152122 Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1 AN XY: 74318

African (AFR) AF: 0.0000724 AC: 3 AN: 41418

American (AMR) AF: 0.00 AC: 0 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3466

East Asian (EAS) AF: 0.000192 AC: 1 AN: 5202

South Asian (SAS) AF: 0.00 AC: 0 AN: 4830

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10608

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.0000294 AC: 2 AN: 68014

Other (OTH) AF: 0.00 AC: 0 AN: 2092

Alfa AF: 0.0000394 Hom.: 0

Bravo AF: 0.0000416

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.099
BayesDel_addAF	Benign	-0.46	T
BayesDel_noAF	Benign	-0.60
CADD	Benign	6.0
DANN	Benign	0.90
DEOGEN2	Benign	0.012	T
Eigen	Benign	-0.97
Eigen_PC	Benign	-0.88
FATHMM_MKL	Benign	0.049	N
LIST_S2	Benign	0.57	T
M_CAP	Benign	0.0030	T
MetaRNN	Benign	0.033	T
MetaSVM	Benign	-0.97	T
MutationAssessor	Benign	-0.34	N
PhyloP100		-0.10
PrimateAI	Benign	0.35	T
PROVEAN	Benign	-1.7	N
REVEL	Benign	0.045
Sift	Benign	0.11	T
Sift4G	Benign	0.064	T
Polyphen		0.16	B
Vest4		0.15
MutPred		0.55		Gain of ubiquitination at K562 (P = 0.0577)
MVP		0.014
ClinPred		0.040	T
GERP RS		-0.14
Varity_R		0.035
gMVP		0.51
Mutation Taster		=98/2	polymorphism

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: rs867818881; hg19: chr11-10874823;