rs6588441

Positions:

• chr1-52757822-G-A
• chr1-52757822-G-C
• chr1-52757822-G-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_024646.3(ZYG11B):​c.196+1199G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.593 in 152,006 control chromosomes in the GnomAD database, including 29,431 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 0.59 (29431 hom., cov: 31)
• Consequence: ZYG11B NM_024646.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.177

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.97).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.949 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZYG11B	NM_024646.3	c.196+1199G>A		intron_variant		ENST00000294353.7	NP_078922.1
ZYG11B	XM_006710898.5	c.184+1199G>A		intron_variant			XP_006710961.1
ZYG11B	XM_017002336.3	c.196+1199G>A		intron_variant			XP_016857825.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZYG11B	ENST00000294353.7	c.196+1199G>A		intron_variant		1	NM_024646.3	ENSP00000294353	P1
ZYG11B	ENST00000545132.5	c.196+1199G>A		intron_variant		2		ENSP00000441315

Frequencies

GnomAD3 genomes AF: 0.592 AC: 89948 AN: 151888 Hom.: 29352 Cov.: 31

Gnomad AFR AF: 0.839

Gnomad AMI AF: 0.493

Gnomad AMR AF: 0.631

Gnomad ASJ AF: 0.542

Gnomad EAS AF: 0.972

Gnomad SAS AF: 0.492

Gnomad FIN AF: 0.502

Gnomad MID AF: 0.516

Gnomad NFE AF: 0.431

Gnomad OTH AF: 0.551

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

GnomAD4 genome AF: 0.593 AC: 90095 AN: 152006 Hom.: 29431 Cov.: 31 AF XY: 0.598 AC XY: 44456 AN XY: 74296

Gnomad4 AFR AF: 0.840

Gnomad4 AMR AF: 0.632

Gnomad4 ASJ AF: 0.542

Gnomad4 EAS AF: 0.972

Gnomad4 SAS AF: 0.491

Gnomad4 FIN AF: 0.502

Gnomad4 NFE AF: 0.431

Gnomad4 OTH AF: 0.557

Alfa AF: 0.514 Hom.: 2719

Bravo AF: 0.618

Asia WGS AF: 0.766 AC: 2664 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	0.91
DANN	Benign	0.22

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: rs6588441; hg19: chr1-53223494;