rs5748218

Variant names:

• chr22-19463663-C-A
• rs5748218
• NM_005659.7:c.495+1539G>T

Your query was ambiguous. Multiple possible variants found:

• chr22-19463663-C-A
• chr22-19463663-C-G
• chr22-19463663-C-T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 5 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005659.7. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	UFD1	NM_005659.7	MANE Select	c.495+1539G>T		intron	N/A	NP_005650.2
	UFD1	NM_001362910.2		c.480+1539G>T		intron	N/A	NP_001349839.1
	UFD1	NM_001035247.3		c.495+1539G>T		intron	N/A	NP_001030324.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	UFD1	ENST00000263202.15	TSL:1 MANE Select	c.495+1539G>T		intron	N/A	ENSP00000263202.9
	UFD1	ENST00000399523.5	TSL:1	c.495+1539G>T		intron	N/A	ENSP00000382439.1
	UFD1	ENST00000459854.5	TSL:1	n.556+1539G>T		intron	N/A

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

African (AFR) AF: 0.865 AC: 35931 AN: 41534

American (AMR) AF: 0.872 AC: 13342 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.859 AC: 2982 AN: 3470

East Asian (EAS) AF: 0.856 AC: 4434 AN: 5180

South Asian (SAS) AF: 0.919 AC: 4439 AN: 4830

European-Finnish (FIN) AF: 0.800 AC: 8473 AN: 10590

Middle Eastern (MID) AF: 0.901 AC: 265 AN: 294

European-Non Finnish (NFE) AF: 0.832 AC: 56562 AN: 68020

Other (OTH) AF: 0.845 AC: 1787 AN: 2114

Alfa AF: 0.842 Hom.: 39657

Bravo AF: 0.850

Asia WGS AF: 0.883 AC: 3070 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	5.6
DANN	Benign	0.59
PhyloP100		0.55
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: rs5748218; hg19: chr22-19451186;