rs4951011

Variant names:

• chr1-203797203-A-G
• rs4951011
• NM_001395895.1:c.-320A>G

Variant summary

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

The NM_001395895.1(ZBED6):​c.-320A>G variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.15 in 178,932 control chromosomes in the GnomAD database, including 2,510 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 0.15 (2079 hom., cov: 32)
  • Exomes 𝑓: 0.17 (431 hom.)
• Consequence: ZBED6 NM_001395895.1 5_prime_UTR_premature_start_codon_gain
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.85
• Publications: 28 publications found

Genes affected

ZBED6 (HGNC:33273): (zinc finger BED-type containing 6) The protein encoded by this transposon-derived intronless gene is a transcriptional repressor that binds to the consensus sequence 5'-GCTCGC-3'. The encoded protein has been shown to repress IGF2 transcription. This gene is located within the first intron of the ZC3H11A gene. [provided by RefSeq, Jul 2016]

ZC3H11A (HGNC:29093): (zinc finger CCCH-type containing 11A) Enables RNA binding activity. Involved in poly(A)+ mRNA export from nucleus. Colocalizes with transcription export complex. [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=-0.81).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.301 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001395895.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZBED6	NM_001395895.1	MANE Select	c.-320A>G		5_prime_UTR_premature_start_codon_gain	Exon 1 of 17	NP_001382824.1
	ZBED6	NM_001395895.1	MANE Select	c.-320A>G		5_prime_UTR	Exon 1 of 17	NP_001382824.1
	ZC3H11A	NM_001376342.1	MANE Select	c.-1588+1409A>G		intron	N/A	NP_001363271.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZBED6	ENST00000550078.3	TSL:1 MANE Select	c.-320A>G		5_prime_UTR_premature_start_codon_gain	Exon 1 of 17	ENSP00000447879.1
	ZBED6	ENST00000550078.3	TSL:1 MANE Select	c.-320A>G		5_prime_UTR	Exon 1 of 17	ENSP00000447879.1
	ZC3H11A	ENST00000367210.3	TSL:1 MANE Select	c.-1588+1409A>G		intron	N/A	ENSP00000356179.1

Frequencies

GnomAD3 genomes AF: 0.147 AC: 22280 AN: 152062 Hom.: 2075 Cov.: 32

Gnomad AFR AF: 0.0607

Gnomad AMI AF: 0.0877

Gnomad AMR AF: 0.262

Gnomad ASJ AF: 0.152

Gnomad EAS AF: 0.313

Gnomad SAS AF: 0.220

Gnomad FIN AF: 0.111

Gnomad MID AF: 0.153

Gnomad NFE AF: 0.161

Gnomad OTH AF: 0.151

GnomAD4 exome AF: 0.167 AC: 4459 AN: 26752 Hom.: 431 Cov.: 0 AF XY: 0.162 AC XY: 2249 AN XY: 13854

African (AFR) AF: 0.0681 AC: 59 AN: 866

American (AMR) AF: 0.265 AC: 364 AN: 1376

Ashkenazi Jewish (ASJ) AF: 0.135 AC: 139 AN: 1030

East Asian (EAS) AF: 0.294 AC: 456 AN: 1552

South Asian (SAS) AF: 0.177 AC: 153 AN: 866

European-Finnish (FIN) AF: 0.129 AC: 134 AN: 1042

Middle Eastern (MID) AF: 0.0794 AC: 10 AN: 126

European-Non Finnish (NFE) AF: 0.158 AC: 2885 AN: 18268

Other (OTH) AF: 0.159 AC: 259 AN: 1626

GnomAD4 genome AF: 0.147 AC: 22300 AN: 152180 Hom.: 2079 Cov.: 32 AF XY: 0.148 AC XY: 11006 AN XY: 74398

African (AFR) AF: 0.0607 AC: 2523 AN: 41540

American (AMR) AF: 0.263 AC: 4018 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.152 AC: 527 AN: 3466

East Asian (EAS) AF: 0.313 AC: 1623 AN: 5178

South Asian (SAS) AF: 0.220 AC: 1061 AN: 4828

European-Finnish (FIN) AF: 0.111 AC: 1176 AN: 10596

Middle Eastern (MID) AF: 0.164 AC: 48 AN: 292

European-Non Finnish (NFE) AF: 0.161 AC: 10927 AN: 67978

Other (OTH) AF: 0.150 AC: 317 AN: 2108

Alfa AF: 0.163 Hom.: 7179

Bravo AF: 0.154

Asia WGS AF: 0.271 AC: 945 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	0.041
DANN	Benign	0.78
PhyloP100		-2.9
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=100/0	polymorphism (auto)

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: rs4951011; hg19: chr1-203766331;