rs4808161

Variant names:

• chr19-18832079-C-G
• rs4808161
• NM_002911.4:c.-131C>G

Your query was ambiguous. Multiple possible variants found:

• chr19-18832079-C-G
• chr19-18832079-C-T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_002911.4(UPF1):​c.-131C>G variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.892 in 819,356 control chromosomes in the GnomAD database, including 326,623 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.91 (63261 hom., cov: 30)
  • Exomes 𝑓: 0.89 (263362 hom.)
• Consequence: UPF1 NM_002911.4 5_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.306
• Publications: 6 publications found

Genes affected

UPF1 (HGNC:9962): (UPF1 RNA helicase and ATPase) This gene encodes a protein that is part of a post-splicing multiprotein complex involved in both mRNA nuclear export and mRNA surveillance. mRNA surveillance detects exported mRNAs with truncated open reading frames and initiates nonsense-mediated mRNA decay (NMD). When translation ends upstream from the last exon-exon junction, this triggers NMD to degrade mRNAs containing premature stop codons. This protein is located only in the cytoplasm. When translation ends, it interacts with the protein that is a functional homolog of yeast Upf2p to trigger mRNA decapping. Use of multiple polyadenylation sites has been noted for this gene. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jul 2014]

UPF1 Gene-Disease associations (from GenCC):

• neurodevelopmental disorder

  Inheritance: AD Classification: MODERATE Submitted by: Ambry Genetics, G2P

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BP6: Variant 19-18832079-C-G is Benign according to our data. Variant chr19-18832079-C-G is described in ClinVar as [Benign]. Clinvar id is 1228122.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.972 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
UPF1	NM_002911.4	c.-131C>G		5_prime_UTR_variant	Exon 1 of 24	ENST00000262803.10	NP_002902.2
UPF1	NM_001297549.2	c.-131C>G		5_prime_UTR_variant	Exon 1 of 24		NP_001284478.1
UPF1	XM_017027105.3	c.-131C>G		5_prime_UTR_variant	Exon 1 of 24		XP_016882594.1
UPF1	XM_017027106.3	c.-131C>G		5_prime_UTR_variant	Exon 1 of 24		XP_016882595.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
UPF1	ENST00000262803.10	c.-131C>G		5_prime_UTR_variant	Exon 1 of 24	1	NM_002911.4	ENSP00000262803.5

Frequencies

GnomAD3 genomes AF: 0.912 AC: 138057 AN: 151308 Hom.: 63199 Cov.: 30

Gnomad AFR AF: 0.980

Gnomad AMI AF: 0.877

Gnomad AMR AF: 0.920

Gnomad ASJ AF: 0.935

Gnomad EAS AF: 0.758

Gnomad SAS AF: 0.852

Gnomad FIN AF: 0.875

Gnomad MID AF: 0.897

Gnomad NFE AF: 0.890

Gnomad OTH AF: 0.925

GnomAD4 exome AF: 0.887 AC: 592464 AN: 667940 Hom.: 263362 Cov.: 9 AF XY: 0.886 AC XY: 295817 AN XY: 333888

African (AFR) AF: 0.983 AC: 12528 AN: 12740

American (AMR) AF: 0.930 AC: 6314 AN: 6790

Ashkenazi Jewish (ASJ) AF: 0.932 AC: 9733 AN: 10444

East Asian (EAS) AF: 0.756 AC: 15789 AN: 20894

South Asian (SAS) AF: 0.850 AC: 22472 AN: 26448

European-Finnish (FIN) AF: 0.881 AC: 20511 AN: 23278

Middle Eastern (MID) AF: 0.885 AC: 1861 AN: 2102

European-Non Finnish (NFE) AF: 0.891 AC: 477877 AN: 536568

Other (OTH) AF: 0.885 AC: 25379 AN: 28676

GnomAD4 genome AF: 0.913 AC: 138176 AN: 151416 Hom.: 63261 Cov.: 30 AF XY: 0.909 AC XY: 67255 AN XY: 73980

African (AFR) AF: 0.980 AC: 40636 AN: 41472

American (AMR) AF: 0.921 AC: 14034 AN: 15246

Ashkenazi Jewish (ASJ) AF: 0.935 AC: 3236 AN: 3462

East Asian (EAS) AF: 0.758 AC: 3851 AN: 5080

South Asian (SAS) AF: 0.851 AC: 4105 AN: 4822

European-Finnish (FIN) AF: 0.875 AC: 9026 AN: 10312

Middle Eastern (MID) AF: 0.910 AC: 264 AN: 290

European-Non Finnish (NFE) AF: 0.890 AC: 60281 AN: 67722

Other (OTH) AF: 0.926 AC: 1947 AN: 2102

Alfa AF: 0.861 Hom.: 2664

Bravo AF: 0.920

Asia WGS AF: 0.828 AC: 2767 AN: 3344

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

May 15, 2021

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	12
DANN	Benign	0.60
PhyloP100		-0.31
PromoterAI		0.12	Neutral
Mutation Taster		=300/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs4808161; hg19: chr19-18942888;