Genetic Variant U2AF1:p.Cys33Cys (chr21-43104348-G-A) – ACMG Classification: Benign (-10 pts)

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_StrongBP6BP7BS2

The NM_006758.3(U2AF1):c.99C>T(p.Cys33Cys) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

Frequency

Genomes: 𝑓 0.0 ( 0 hom., cov: 0)

Exomes 𝑓: 0.0011 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

U2AF1
NM_006758.3 synonymous

Scores

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: 2.64

Publications

1 publications found

Variant links:

Genes affected

U2AF1 (HGNC:12453): (U2 small nuclear RNA auxiliary factor 1) This gene belongs to the splicing factor SR family of genes. U2 auxiliary factor, comprising a large and a small subunit, is a non-snRNP protein required for the binding of U2 snRNP to the pre-mRNA branch site. This gene encodes the small subunit which plays a critical role in both constitutive and enhancer-dependent RNA splicing by directly mediating interactions between the large subunit and proteins bound to the enhancers. Alternatively spliced transcript variants encoding different isoforms have been identified. [provided by RefSeq, Jul 2008]

U2AF1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -10 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.47).

BP6

Variant 21-43104348-G-A is Benign according to our data. Variant chr21-43104348-G-A is described in ClinVar as Benign. ClinVar VariationId is 3053298.Status of the report is no_assertion_criteria_provided, 0 stars.

BP7

Synonymous conserved (PhyloP=2.64 with no splicing effect.

BS2

High AC in GnomAdExome4 at 19 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006758.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
U2AF1	NM_006758.3	MANE Select	c.99C>T	p.Cys33Cys	synonymous	Exon 2 of 8	NP_006749.1	Q01081-1
U2AF1	NM_001025203.1		c.99C>T	p.Cys33Cys	synonymous	Exon 2 of 8	NP_001020374.1	Q01081-2
U2AF1	NM_001025204.2		c.-188C>T		5_prime_UTR	Exon 2 of 9	NP_001020375.1	Q01081-4

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
U2AF1	ENST00000291552.9	TSL:1 MANE Select	c.99C>T	p.Cys33Cys	synonymous	Exon 2 of 8	ENSP00000291552.4	Q01081-1
U2AF1	ENST00000380276.6	TSL:1	c.99C>T	p.Cys33Cys	synonymous	Exon 2 of 8	ENSP00000369629.2	Q01081-2
U2AF1	ENST00000459639.5	TSL:1	c.-121C>T		5_prime_UTR	Exon 1 of 7	ENSP00000418705.1	Q01081-4

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

AN:

1004

Hom.:

Cov.:

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.000788

AC:

197

AN:

249888

AF XY:

0.000777

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000234

Gnomad ASJ exome

AF:

0.0162

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000159

Gnomad OTH exome

AF:

0.00131

GnomAD4 exome

AF:

0.00106

AC:

AN:

17932

Hom.:

Cov.:

AF XY:

0.00133

AC XY:

AN XY:

9054

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

564

American (AMR)

AF:

0.00

AC:

AN:

328

Ashkenazi Jewish (ASJ)

AF:

0.0210

AC:

AN:

808

East Asian (EAS)

AF:

0.00

AC:

AN:

2188

South Asian (SAS)

AF:

0.00

AC:

AN:

468

European-Finnish (FIN)

AF:

0.00

AC:

AN:

810

Middle Eastern (MID)

AF:

0.00

AC:

AN:

European-Non Finnish (NFE)

AF:

0.0000871

AC:

AN:

11484

Other (OTH)

AF:

0.000826

AC:

AN:

1210

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.520

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<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

Data not reliable, filtered out with message: AC0;AS_VQSR

AF:

0.00

AC:

AN:

1004

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

508

African (AFR)

AF:

0.00

AC:

AN:

144

American (AMR)

AF:

0.00

AC:

AN:

140

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

East Asian (EAS)

AF:

0.00

AC:

AN:

190

South Asian (SAS)

AF:

0.00

AC:

AN:

106

European-Finnish (FIN)

AF:

0.00

AC:

AN:

Middle Eastern (MID)

AF:

0.00

AC:

AN:

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

356

Other (OTH)

AF:

0.00

AC:

AN:

Alfa

AF:

0.00157

Hom.:

ClinVar

ClinVar submissions

Significance:Benign

Revision:no assertion criteria provided

View on ClinVar

Pathogenic

VUS

Benign

Condition

U2AF1-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.47

CADD

Benign

(source)

DANN

Benign

0.91

PhyloP100

2.6

Mutation Taster

=271/29

polymorphism

(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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over