rs17638853

chr19-35743751-T-C

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BA1

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.143

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]

ACMG classification

Verdict is Benign. Variant got -8 ACMG points.

• 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/exons	MANE	UniProt
U2AF1L4	NM_001040425.3	c.461+58A>G		intron_variant		ENST00000378975.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
U2AF1L4	ENST00000378975.8	c.461+58A>G		intron_variant		1	NM_001040425.3

Frequencies

GnomAD3 genomes AF: 0.0502 AC: 7525 AN: 149876 Hom.: 238 Cov.: 31

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

GnomAD3 exomes AF: 0.0556 AC: 10414 AN: 187316 Hom.: 337 AF XY: 0.0582 AC XY: 5848 AN XY: 100438

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 SAS exome AF: 0.0873

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.: 19 AF XY: 0.0621 AC XY: 35672 AN XY: 574066

Gnomad4 AFR exome AF: 0.0475

Gnomad4 AMR exome AF: 0.0321

Gnomad4 ASJ exome AF: 0.134

Gnomad4 EAS exome AF: 0.0159

Gnomad4 SAS exome AF: 0.0885

Gnomad4 FIN exome AF: 0.0430

Gnomad4 NFE exome AF: 0.0616

Gnomad4 OTH exome AF: 0.0629

GnomAD4 genome AF: 0.0502 AC: 7530 AN: 149926 Hom.: 239 Cov.: 31 AF XY: 0.0506 AC XY: 3699 AN XY: 73040

Gnomad4 AFR AF: 0.0406

Gnomad4 AMR AF: 0.0392

Gnomad4 ASJ AF: 0.138

Gnomad4 EAS AF: 0.0223

Gnomad4 SAS AF: 0.0929

Gnomad4 FIN AF: 0.0450

Gnomad4 NFE AF: 0.0531

Gnomad4 OTH AF: 0.0530

Alfa AF: 0.0552 Hom.: 145

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
Dann	Benign	0.69

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

LitVar

Other links and lift over

dbSNP: rs17638853; hg19: chr19-36234652; COSMIC: COSV53073802; COSMIC: COSV53073802;