rs4951011

Positions:

• chr1-203797203-A-G

Variant summary

Our verdict is Benign. Variant got -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

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]

ZC3H11A (HGNC:):

ACMG classification

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZBED6	NM_001395895.1	c.-320A>G		5_prime_UTR_premature_start_codon_gain_variant	1/17	ENST00000550078.3	NP_001382824.1
ZBED6	NM_001395895.1	c.-320A>G		5_prime_UTR_variant	1/17	ENST00000550078.3	NP_001382824.1
ZC3H11A	NM_001376342.1	c.-1588+1409A>G		intron_variant		ENST00000367210.3	NP_001363271.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZBED6	ENST00000550078	c.-320A>G		5_prime_UTR_premature_start_codon_gain_variant	1/17	1	NM_001395895.1	ENSP00000447879.1
ZBED6	ENST00000550078	c.-320A>G		5_prime_UTR_variant	1/17	1	NM_001395895.1	ENSP00000447879.1
ZC3H11A	ENST00000367210.3	c.-1588+1409A>G		intron_variant		1	NM_001376342.1	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

Gnomad4 AFR exome AF: 0.0681

Gnomad4 AMR exome AF: 0.265

Gnomad4 ASJ exome AF: 0.135

Gnomad4 EAS exome AF: 0.294

Gnomad4 SAS exome AF: 0.177

Gnomad4 FIN exome AF: 0.129

Gnomad4 NFE exome AF: 0.158

Gnomad4 OTH exome AF: 0.159

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

Gnomad4 AFR AF: 0.0607

Gnomad4 AMR AF: 0.263

Gnomad4 ASJ AF: 0.152

Gnomad4 EAS AF: 0.313

Gnomad4 SAS AF: 0.220

Gnomad4 FIN AF: 0.111

Gnomad4 NFE AF: 0.161

Gnomad4 OTH AF: 0.150

Alfa AF: 0.163 Hom.: 3158

Bravo AF: 0.154

Asia WGS AF: 0.271 AC: 945 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	0.041
DANN	Benign	0.78
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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: rs4951011; hg19: chr1-203766331;