rs5748219

Positions:

• chr22-19463745-G-C

Variant summary

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

The NM_005659.7(UFD1):​c.495+1457C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.52 in 152,084 control chromosomes in the GnomAD database, including 20,696 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 0.52 (20696 hom., cov: 33)
• Consequence: UFD1 NM_005659.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.41

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=-0.95).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.587 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
UFD1	NM_005659.7	c.495+1457C>G		intron_variant		ENST00000263202.15

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
UFD1	ENST00000263202.15	c.495+1457C>G		intron_variant		1	NM_005659.7	P1

Frequencies

GnomAD3 genomes AF: 0.520 AC: 78988 AN: 151966 Hom.: 20674 Cov.: 33

Gnomad AFR AF: 0.509

Gnomad AMI AF: 0.546

Gnomad AMR AF: 0.509

Gnomad ASJ AF: 0.622

Gnomad EAS AF: 0.381

Gnomad SAS AF: 0.605

Gnomad FIN AF: 0.480

Gnomad MID AF: 0.570

Gnomad NFE AF: 0.533

Gnomad OTH AF: 0.532

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

GnomAD4 genome AF: 0.520 AC: 79048 AN: 152084 Hom.: 20696 Cov.: 33 AF XY: 0.517 AC XY: 38463 AN XY: 74336

Gnomad4 AFR AF: 0.509

Gnomad4 AMR AF: 0.509

Gnomad4 ASJ AF: 0.622

Gnomad4 EAS AF: 0.381

Gnomad4 SAS AF: 0.605

Gnomad4 FIN AF: 0.480

Gnomad4 NFE AF: 0.533

Gnomad4 OTH AF: 0.538

Alfa AF: 0.524 Hom.: 2630

Bravo AF: 0.516

Asia WGS AF: 0.503 AC: 1749 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.85
DANN	Benign	0.52

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: rs5748219; hg19: chr22-19451268;