chr19-35743751-T-C

Variant names:

• chr19-35743751-T-C
• rs17638853
• NM_001040425.3:c.461+58A>G

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 2P and 8B. PP3_Moderate 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
• Publications: 8 publications found

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]

ENSG00000267120 (HGNC:):

ACMG classification

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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001040425.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	U2AF1L4	NM_001040425.3	MANE Select	c.461+58A>G		intron	N/A	NP_001035515.1
	U2AF1L4	NM_144987.4		c.403+58A>G		intron	N/A	NP_659424.2
	U2AF1L4	NM_001369824.2		c.403+58A>G		intron	N/A	NP_001356753.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	U2AF1L4	ENST00000378975.8	TSL:1 MANE Select	c.461+58A>G		intron	N/A	ENSP00000368258.2
	U2AF1L4	ENST00000292879.9	TSL:1	c.403+58A>G		intron	N/A	ENSP00000292879.4
	U2AF1L4	ENST00000587987.5	TSL:1	n.*429+58A>G		intron	N/A	ENSP00000465170.1

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

GnomAD2 exomes AF: 0.0556 AC: 10414 AN: 187316 AF XY: 0.0582

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

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

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

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: 25 AN: 292

European-Non Finnish (NFE) AF: 0.0531 AC: 3589 AN: 67616

Other (OTH) AF: 0.0530 AC: 109 AN: 2058

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	3.8
DANN	Benign	0.69
PhyloP100		-0.14
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

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