14-20699896-T-A

Variant names:

• chr14-20699896-T-A
• rs3094
• NM_002937.5:c.*81T>A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_002937.5(RNASE4):​c.*81T>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000279 in 1,074,494 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: 32)
  • Exomes 𝑓: 0.0000028 (0 hom.)
• Consequence: RNASE4 NM_002937.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.182
• Publications: 18 publications found

Genes affected

RNASE4 (HGNC:10047): (ribonuclease A family member 4) The protein encoded by this gene belongs to the pancreatic ribonuclease family. It plays an important role in mRNA cleavage and has marked specificity towards the 3' side of uridine nucleotides. Alternative splicing results in four transcript variants encoding the same protein. This gene and the gene that encodes angiogenin share promoters and 5' exons. Each gene splices to a unique downstream exon that contains its complete coding region. [provided by RefSeq, Aug 2013]

ENSG00000259171 (HGNC:):

EGILA (HGNC:54482): (EGFR interacting lncRNA)

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.63).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RNASE4	NM_002937.5	c.*81T>A		3_prime_UTR_variant	Exon 2 of 2	ENST00000555835.3	NP_002928.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RNASE4	ENST00000555835.3	c.*81T>A		3_prime_UTR_variant	Exon 2 of 2	1	NM_002937.5	ENSP00000452245.1
ENSG00000259171	ENST00000553909.1	c.*532T>A		3_prime_UTR_variant	Exon 3 of 3	2		ENSP00000477037.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000279 AC: 3 AN: 1074494 Hom.: 0 Cov.: 14 AF XY: 0.00 AC XY: 0 AN XY: 542888

African (AFR) AF: 0.00 AC: 0 AN: 25912

American (AMR) AF: 0.00 AC: 0 AN: 39744

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 20298

East Asian (EAS) AF: 0.00 AC: 0 AN: 37562

South Asian (SAS) AF: 0.00 AC: 0 AN: 69312

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 49814

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4426

European-Non Finnish (NFE) AF: 0.00000384 AC: 3 AN: 780336

Other (OTH) AF: 0.00 AC: 0 AN: 47090

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 9889

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.63
CADD	Benign	7.2
DANN	Benign	0.86
PhyloP100		-0.18

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: rs3094; hg19: chr14-21168055;