rs5748218

chr22-19463663-C-Achr22-19463663-C-Gchr22-19463663-C-T

Variant summary

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

The NM_005659.7(UFD1):c.495+1539G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.847 in 152,244 control chromosomes in the GnomAD database, including 54,684 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 0.85 (54684 hom., cov: 33)
• Consequence: UFD1 NM_005659.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.548

Genes affected

UFD1 (HGNC:12520): (ubiquitin recognition factor in ER associated degradation 1) The protein encoded by this gene forms a complex with two other proteins, nuclear protein localization-4 and valosin-containing protein, and this complex is necessary for the degradation of ubiquitinated proteins. In addition, this complex controls the disassembly of the mitotic spindle and the formation of a closed nuclear envelope after mitosis. Mutations in this gene have been associated with Catch 22 syndrome as well as cardiac and craniofacial defects. Alternative splicing results in multiple transcript variants encoding different isoforms. A related pseudogene has been identified on chromosome 18. [provided by RefSeq, Jun 2009]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.896 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
UFD1	NM_005659.7	c.495+1539G>T		intron_variant		ENST00000263202.15

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
UFD1	ENST00000263202.15	c.495+1539G>T		intron_variant		1	NM_005659.7	P1

Frequencies

GnomAD3 genomes AF: 0.847 AC: 128880 AN: 152126 Hom.: 54641 Cov.: 33

Gnomad AFR AF: 0.865

Gnomad AMI AF: 0.836

Gnomad AMR AF: 0.872

Gnomad ASJ AF: 0.859

Gnomad EAS AF: 0.856

Gnomad SAS AF: 0.919

Gnomad FIN AF: 0.800

Gnomad MID AF: 0.908

Gnomad NFE AF: 0.832

Gnomad OTH AF: 0.843

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

GnomAD4 genome AF: 0.847 AC: 128977 AN: 152244 Hom.: 54684 Cov.: 33 AF XY: 0.847 AC XY: 63062 AN XY: 74414

Gnomad4 AFR AF: 0.865

Gnomad4 AMR AF: 0.872

Gnomad4 ASJ AF: 0.859

Gnomad4 EAS AF: 0.856

Gnomad4 SAS AF: 0.919

Gnomad4 FIN AF: 0.800

Gnomad4 NFE AF: 0.832

Gnomad4 OTH AF: 0.845

Alfa AF: 0.842 Hom.: 27796

Bravo AF: 0.850

Asia WGS AF: 0.883 AC: 3070 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
Cadd	Benign	5.6
Dann	Benign	0.59

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: rs5748218; hg19: chr22-19451186;