rs6662414

Variant names:

• chr1-52733221-A-G
• rs6662414
• NM_024646.3:c.30+6538A>G

Variant summary

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

The NM_024646.3(ZYG11B):​c.30+6538A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.488 in 152,010 control chromosomes in the GnomAD database, including 18,386 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 0.49 (18386 hom., cov: 32)
• Consequence: ZYG11B NM_024646.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.218
• Publications: 4 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=-0.83).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.606 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZYG11B	NM_024646.3	c.30+6538A>G		intron_variant	Intron 1 of 13	ENST00000294353.7	NP_078922.1
ZYG11B	NM_001441954.1	c.-101+6538A>G		intron_variant	Intron 1 of 14		NP_001428883.1
ZYG11B	NR_199864.1	n.231+6538A>G		intron_variant	Intron 1 of 15

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZYG11B	ENST00000294353.7	c.30+6538A>G		intron_variant	Intron 1 of 13	1	NM_024646.3	ENSP00000294353.6
ZYG11B	ENST00000545132.5	c.30+6538A>G		intron_variant	Intron 1 of 13	2		ENSP00000441315.1

Frequencies

GnomAD3 genomes AF: 0.488 AC: 74060 AN: 151892 Hom.: 18350 Cov.: 32

Gnomad AFR AF: 0.432

Gnomad AMI AF: 0.512

Gnomad AMR AF: 0.565

Gnomad ASJ AF: 0.539

Gnomad EAS AF: 0.625

Gnomad SAS AF: 0.469

Gnomad FIN AF: 0.561

Gnomad MID AF: 0.541

Gnomad NFE AF: 0.481

Gnomad OTH AF: 0.480

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

GnomAD4 genome AF: 0.488 AC: 74148 AN: 152010 Hom.: 18386 Cov.: 32 AF XY: 0.495 AC XY: 36810 AN XY: 74300

African (AFR) AF: 0.432 AC: 17906 AN: 41442

American (AMR) AF: 0.566 AC: 8634 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.539 AC: 1873 AN: 3472

East Asian (EAS) AF: 0.624 AC: 3226 AN: 5166

South Asian (SAS) AF: 0.468 AC: 2255 AN: 4818

European-Finnish (FIN) AF: 0.561 AC: 5929 AN: 10566

Middle Eastern (MID) AF: 0.548 AC: 161 AN: 294

European-Non Finnish (NFE) AF: 0.481 AC: 32680 AN: 67976

Other (OTH) AF: 0.484 AC: 1018 AN: 2102

Alfa AF: 0.478 Hom.: 5219

Bravo AF: 0.487

Asia WGS AF: 0.573 AC: 1993 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	8.3
DANN	Benign	0.88
PhyloP100		0.22
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: rs6662414; hg19: chr1-53198893;