rs8137166

Variant names:

• chr22-19450821-G-A
• rs8137166
• NM_005659.7:c.850-77C>T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_005659.7(UFD1):​c.850-77C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0162 in 1,606,858 control chromosomes in the GnomAD database, including 3,463 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.085 (1825 hom., cov: 31)
  • Exomes 𝑓: 0.0090 (1638 hom.)
• Consequence: UFD1 NM_005659.7 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.938
• Publications: 0 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]

UFD1-AS1 (HGNC:55917): (UFD1 antisense RNA 1)

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BP6: Variant 22-19450821-G-A is Benign according to our data. Variant chr22-19450821-G-A is described in ClinVar as Benign. ClinVar VariationId is 1236720.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.29 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	UFD1	NM_005659.7	MANE Select	c.850-77C>T		intron	N/A	NP_005650.2
	UFD1	NM_001362910.2		c.835-77C>T		intron	N/A	NP_001349839.1
	UFD1	NM_001035247.3		c.797-77C>T		intron	N/A	NP_001030324.2	Q92890-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	UFD1	ENST00000263202.15	TSL:1 MANE Select	c.850-77C>T		intron	N/A	ENSP00000263202.9	Q92890-2
	UFD1	ENST00000399523.5	TSL:1	c.797-77C>T		intron	N/A	ENSP00000382439.1	Q92890-3
	UFD1	ENST00000459854.5	TSL:1	n.4838C>T		non_coding_transcript_exon	Exon 11 of 11

Frequencies

GnomAD3 genomes AF: 0.0853 AC: 12951 AN: 151908 Hom.: 1822 Cov.: 31

Gnomad AFR AF: 0.295

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0346

Gnomad ASJ AF: 0.00317

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.00186

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0127

Gnomad NFE AF: 0.00132

Gnomad OTH AF: 0.0665

GnomAD4 exome AF: 0.00895 AC: 13028 AN: 1454832 Hom.: 1638 Cov.: 30 AF XY: 0.00773 AC XY: 5592 AN XY: 723162

African (AFR) AF: 0.300 AC: 10003 AN: 33292

American (AMR) AF: 0.0195 AC: 866 AN: 44344

Ashkenazi Jewish (ASJ) AF: 0.00332 AC: 86 AN: 25906

East Asian (EAS) AF: 0.00 AC: 0 AN: 39520

South Asian (SAS) AF: 0.000628 AC: 54 AN: 86000

European-Finnish (FIN) AF: 0.0000382 AC: 2 AN: 52372

Middle Eastern (MID) AF: 0.0152 AC: 87 AN: 5736

European-Non Finnish (NFE) AF: 0.000628 AC: 696 AN: 1107648

Other (OTH) AF: 0.0206 AC: 1234 AN: 60014

GnomAD4 genome AF: 0.0853 AC: 12974 AN: 152026 Hom.: 1825 Cov.: 31 AF XY: 0.0821 AC XY: 6105 AN XY: 74340

African (AFR) AF: 0.295 AC: 12192 AN: 41390

American (AMR) AF: 0.0346 AC: 529 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.00317 AC: 11 AN: 3472

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5176

South Asian (SAS) AF: 0.00166 AC: 8 AN: 4828

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10558

Middle Eastern (MID) AF: 0.0136 AC: 4 AN: 294

European-Non Finnish (NFE) AF: 0.00132 AC: 90 AN: 67996

Other (OTH) AF: 0.0658 AC: 139 AN: 2112

Alfa AF: 0.0882 Hom.: 336

Bravo AF: 0.0971

Asia WGS AF: 0.0170 AC: 59 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	8.8
DANN	Benign	0.72
PhyloP100		0.94
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: rs8137166; hg19: chr22-19438344;