rs950182

Variant names:

• chr1-52801608-A-G
• rs950182
• NM_024646.3:c.1486-211A>G

Your query was ambiguous. Multiple possible variants found:

• chr1-52801608-A-G
• chr1-52801608-A-T

Variant summary

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

The NM_024646.3(ZYG11B):​c.1486-211A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.144 in 152,018 control chromosomes in the GnomAD database, including 3,749 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 0.14 (3749 hom., cov: 32)
• Consequence: ZYG11B NM_024646.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.00300
• Publications: 1 publications found

Genes affected

ZYG11B (HGNC:25820): (zyg-11 family member B, cell cycle regulator) Involved in positive regulation of proteasomal ubiquitin-dependent protein catabolic process and protein quality control for misfolded or incompletely synthesized proteins. Part of Cul2-RING ubiquitin ligase complex. [provided by Alliance of Genome Resources, Apr 2022]

ZYG11B Gene-Disease associations (from GenCC):

• multiple congenital anomalies/dysmorphic syndrome

  Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.394 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZYG11B	NM_024646.3	c.1486-211A>G		intron_variant	Intron 8 of 13	ENST00000294353.7	NP_078922.1
ZYG11B	NM_001441954.1	c.1474-211A>G		intron_variant	Intron 9 of 14		NP_001428883.1
ZYG11B	NR_199864.1	n.1687-211A>G		intron_variant	Intron 8 of 15

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZYG11B	ENST00000294353.7	c.1486-211A>G		intron_variant	Intron 8 of 13	1	NM_024646.3	ENSP00000294353.6
ZYG11B	ENST00000545132.5	c.1486-211A>G		intron_variant	Intron 8 of 13	2		ENSP00000441315.1

Frequencies

GnomAD3 genomes AF: 0.143 AC: 21787 AN: 151900 Hom.: 3741 Cov.: 32

Gnomad AFR AF: 0.399

Gnomad AMI AF: 0.0340

Gnomad AMR AF: 0.102

Gnomad ASJ AF: 0.0317

Gnomad EAS AF: 0.345

Gnomad SAS AF: 0.0916

Gnomad FIN AF: 0.00679

Gnomad MID AF: 0.0475

Gnomad NFE AF: 0.0155

Gnomad OTH AF: 0.112

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

GnomAD4 genome AF: 0.144 AC: 21825 AN: 152018 Hom.: 3749 Cov.: 32 AF XY: 0.142 AC XY: 10538 AN XY: 74352

African (AFR) AF: 0.399 AC: 16526 AN: 41394

American (AMR) AF: 0.102 AC: 1556 AN: 15258

Ashkenazi Jewish (ASJ) AF: 0.0317 AC: 110 AN: 3470

East Asian (EAS) AF: 0.345 AC: 1789 AN: 5182

South Asian (SAS) AF: 0.0909 AC: 439 AN: 4832

European-Finnish (FIN) AF: 0.00679 AC: 72 AN: 10598

Middle Eastern (MID) AF: 0.0442 AC: 13 AN: 294

European-Non Finnish (NFE) AF: 0.0155 AC: 1051 AN: 67972

Other (OTH) AF: 0.113 AC: 238 AN: 2106

Alfa AF: 0.0284 Hom.: 86

Bravo AF: 0.164

Asia WGS AF: 0.218 AC: 756 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	1.3
DANN	Benign	0.67
PhyloP100		0.0030
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: rs950182; hg19: chr1-53267280;