rs17638853

Variant names:

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

Your query was ambiguous. Multiple possible variants found:

• chr19-35743751-T-A
• chr19-35743751-T-C

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001040425.3(U2AF1L4):​c.461+58A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000351 in 1,138,020 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 31)
  • Exomes 𝑓: 0.0000035 (0 hom.)
• Consequence: U2AF1L4 NM_001040425.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.143
• Publications: 0 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: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (REVEL=0.026).

Transcripts

RefSeq

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

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 0.00000351 AC: 4 AN: 1138020 Hom.: 0 Cov.: 19 AF XY: 0.00000348 AC XY: 2 AN XY: 574236

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.0000373 AC: 1 AN: 26794

American (AMR) AF: 0.00 AC: 0 AN: 37128

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 23374

East Asian (EAS) AF: 0.00 AC: 0 AN: 35188

South Asian (SAS) AF: 0.00 AC: 0 AN: 76194

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 48390

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5056

European-Non Finnish (NFE) AF: 0.00000359 AC: 3 AN: 836428

Other (OTH) AF: 0.00 AC: 0 AN: 49468

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.76
CADD	Benign	3.4
DANN	Benign	0.82
PhyloP100		-0.14

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

Other links and lift over

dbSNP: rs17638853; hg19: chr19-36234652;