dbSNP rs5748212: UFD1:c.678+179C>A (chr22-19456408-G-T) – ACMG Classification: Benign (-20 pts)

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_005659.7(UFD1):c.678+179C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0384 in 757,744 control chromosomes in the GnomAD database, including 1,085 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.049 ( 283 hom., cov: 32)

Exomes 𝑓: 0.036 ( 802 hom. )

Consequence

UFD1
NM_005659.7 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.734

Publications

1 publications found

Variant links:

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 links:

ENSG00000273212 (HGNC:):

ENSG00000273212 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.9).

BP6

Variant 22-19456408-G-T is Benign according to our data. Variant chr22-19456408-G-T is described in ClinVar as Benign. ClinVar VariationId is 1253888.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.109 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

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
UFD1	NM_005659.7	MANE Select	c.678+179C>A	intron	N/A	NP_005650.2
UFD1	NM_001362910.2		c.663+179C>A	intron	N/A	NP_001349839.1
UFD1	NM_001035247.3		c.678+179C>A	intron	N/A	NP_001030324.2	Q92890-3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
UFD1	ENST00000263202.15	TSL:1 MANE Select	c.678+179C>A	intron	N/A	ENSP00000263202.9	Q92890-2
UFD1	ENST00000399523.5	TSL:1	c.678+179C>A	intron	N/A	ENSP00000382439.1	Q92890-3
UFD1	ENST00000459854.5	TSL:1	n.739+179C>A	intron	N/A

Frequencies

GnomAD3 genomes

AF:

0.0493

AC:

7498

AN:

152088

Hom.:

281

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0823

Gnomad AMI

AF:

0.00219

Gnomad AMR

AF:

0.0779

Gnomad ASJ

AF:

0.0153

Gnomad EAS

AF:

0.117

Gnomad SAS

AF:

0.0961

Gnomad FIN

AF:

0.0534

Gnomad MID

AF:

0.00949

Gnomad NFE

AF:

0.0166

Gnomad OTH

AF:

0.0368

GnomAD4 exome

AF:

0.0356

AC:

21576

AN:

605538

Hom.:

802

AF XY:

0.0372

AC XY:

11790

AN XY:

317148

show subpopulations

African (AFR)

AF:

0.0830

AC:

1335

AN:

16086

American (AMR)

AF:

0.102

AC:

2505

AN:

24624

Ashkenazi Jewish (ASJ)

AF:

0.0171

AC:

267

AN:

15632

East Asian (EAS)

AF:

0.111

AC:

3663

AN:

33148

South Asian (SAS)

AF:

0.0861

AC:

4551

AN:

52878

European-Finnish (FIN)

AF:

0.0405

AC:

1501

AN:

37086

Middle Eastern (MID)

AF:

0.0106

AC:

AN:

2818

European-Non Finnish (NFE)

AF:

0.0169

AC:

6621

AN:

391660

Other (OTH)

AF:

0.0349

AC:

1103

AN:

31606

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.507

Heterozygous variant carriers

1011

2022

3032

4043

5054

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

214

428

642

856

1070

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0493

AC:

7508

AN:

152206

Hom.:

283

Cov.:

AF XY:

0.0528

AC XY:

3928

AN XY:

74436

show subpopulations

African (AFR)

AF:

0.0823

AC:

3419

AN:

41520

American (AMR)

AF:

0.0782

AC:

1195

AN:

15280

Ashkenazi Jewish (ASJ)

AF:

0.0153

AC:

AN:

3468

East Asian (EAS)

AF:

0.117

AC:

605

AN:

5176

South Asian (SAS)

AF:

0.0956

AC:

461

AN:

4822

European-Finnish (FIN)

AF:

0.0534

AC:

566

AN:

10608

Middle Eastern (MID)

AF:

0.0102

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0166

AC:

1127

AN:

68012

Other (OTH)

AF:

0.0364

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

338

676

1015

1353

1691

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

176

264

352

440

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0265

Hom.:

136

Bravo

AF:

0.0520

Asia WGS

AF:

0.107

AC:

371

AN:

3478

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.90

CADD

Benign

0.20

(source)

DANN

Benign

0.50

PhyloP100

-0.73

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over