Genetic Variant U2AF1L4:c.461+58A>G (chr19-35743751-T-C) – ACMG Classification: Likely_benign (-6 pts)

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 2P and 8B. PP3_ModerateBA1

The NM_001040425.3(U2AF1L4):c.461+58A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0602 in 1,287,570 control chromosomes in the GnomAD database, including 2,441 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 0.050 ( 239 hom., cov: 31)

Exomes 𝑓: 0.062 ( 2202 hom. )

Consequence

U2AF1L4
NM_001040425.3 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.143

Publications

8 publications found

Variant links:

Genes affected

U2AF1L4 (HGNC:23020): (U2 small nuclear RNA auxiliary factor 1 like 4) Predicted to enable pre-mRNA 3'-splice site binding activity. Predicted to be involved in mRNA splicing, via spliceosome. Predicted to be located in nucleoplasm. Predicted to be part of U2AF complex and spliceosomal complex. [provided by Alliance of Genome Resources, Apr 2022]

U2AF1L4 links:

ENSG00000267120 (HGNC:):

ENSG00000267120 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -6 ACMG points.

PP3

Splicing predictors support a deleterious effect. Scorers claiming Pathogenic: max_spliceai. No scorers claiming Uncertain. No scorers claiming Benign.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.0858 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
U2AF1L4	NM_001040425.3 link	c.461+58A>G		intron_variant	Intron 5 of 5	ENST00000378975.8	NP_001035515.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
U2AF1L4	ENST00000378975.8 link	c.461+58A>G		intron_variant	Intron 5 of 5	1	NM_001040425.3	ENSP00000368258.2
ENSG00000267120	ENST00000589807.1 link	n.*222+58A>G		intron_variant	Intron 6 of 10	2		ENSP00000472696.1

Frequencies

GnomAD3 genomes

AF:

0.0502

AC:

7525

AN:

149876

Hom.:

238

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0405

Gnomad AMI

AF:

0.0938

Gnomad AMR

AF:

0.0393

Gnomad ASJ

AF:

0.138

Gnomad EAS

AF:

0.0222

Gnomad SAS

AF:

0.0926

Gnomad FIN

AF:

0.0450

Gnomad MID

AF:

0.0764

Gnomad NFE

AF:

0.0531

Gnomad OTH

AF:

0.0537

GnomAD2 exomes

AF:

0.0556

AC:

10414

AN:

187316

AF XY:

0.0582

show subpopulations

Gnomad AFR exome

AF:

0.0427

Gnomad AMR exome

AF:

0.0306

Gnomad ASJ exome

AF:

0.132

Gnomad EAS exome

AF:

0.0262

Gnomad FIN exome

AF:

0.0429

Gnomad NFE exome

AF:

0.0548

Gnomad OTH exome

AF:

0.0595

GnomAD4 exome

AF:

0.0615

AC:

69999

AN:

1137644

Hom.:

2202

Cov.:

AF XY:

0.0621

AC XY:

35672

AN XY:

574066

show subpopulations

African (AFR)

AF:

0.0475

AC:

1273

AN:

26786

American (AMR)

AF:

0.0321

AC:

1192

AN:

37126

Ashkenazi Jewish (ASJ)

AF:

0.134

AC:

3123

AN:

23358

East Asian (EAS)

AF:

0.0159

AC:

561

AN:

35190

South Asian (SAS)

AF:

0.0885

AC:

6741

AN:

76178

European-Finnish (FIN)

AF:

0.0430

AC:

2080

AN:

48378

Middle Eastern (MID)

AF:

0.0892

AC:

451

AN:

5054

European-Non Finnish (NFE)

AF:

0.0616

AC:

51468

AN:

836112

Other (OTH)

AF:

0.0629

AC:

3110

AN:

49462

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.513

Heterozygous variant carriers

3479

6958

10438

13917

17396

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

1914

3828

5742

7656

9570

<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:

0.0502

AC:

7530

AN:

149926

Hom.:

239

Cov.:

AF XY:

0.0506

AC XY:

3699

AN XY:

73040

show subpopulations

African (AFR)

AF:

0.0406

AC:

1653

AN:

40756

American (AMR)

AF:

0.0392

AC:

591

AN:

15072

Ashkenazi Jewish (ASJ)

AF:

0.138

AC:

477

AN:

3458

East Asian (EAS)

AF:

0.0223

AC:

113

AN:

5072

South Asian (SAS)

AF:

0.0929

AC:

439

AN:

4724

European-Finnish (FIN)

AF:

0.0450

AC:

449

AN:

9972

Middle Eastern (MID)

AF:

0.0856

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.0531

AC:

3589

AN:

67616

Other (OTH)

AF:

0.0530

AC:

109

AN:

2058

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

341

681

1022

1362

1703

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

180

270

360

450

<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:

0.0527

Hom.:

446

Bravo

AF:

0.0479

Asia WGS

AF:

0.0440

AC:

153

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.80

CADD

Benign

3.8

(source)

DANN

Benign

0.69

PhyloP100

-0.14

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.95

Details are displayed if max score is > 0.2

DS_DG_spliceai

0.95

Position offset: 1

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over