14-20699896-T-C

Position:

• chr14-20699896-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_002937.5(RNASE4):​c.*81T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.23 in 1,224,690 control chromosomes in the GnomAD database, including 35,962 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 0.19 (3448 hom., cov: 32)
  • Exomes 𝑓: 0.24 (32514 hom.)
• Consequence: RNASE4 NM_002937.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.182

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:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.67).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.451 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RNASE4	NM_002937.5	c.*81T>C		3_prime_UTR_variant	2/2	ENST00000555835.3	NP_002928.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RNASE4	ENST00000555835.3	c.*81T>C		3_prime_UTR_variant	2/2	1	NM_002937.5	ENSP00000452245.1
ENSG00000259171	ENST00000553909.1	c.*532T>C		3_prime_UTR_variant	3/3	2		ENSP00000477037.1

Frequencies

GnomAD3 genomes AF: 0.188 AC: 28594 AN: 152036 Hom.: 3453 Cov.: 32

Gnomad AFR AF: 0.0495

Gnomad AMI AF: 0.106

Gnomad AMR AF: 0.185

Gnomad ASJ AF: 0.164

Gnomad EAS AF: 0.467

Gnomad SAS AF: 0.203

Gnomad FIN AF: 0.242

Gnomad MID AF: 0.174

Gnomad NFE AF: 0.244

Gnomad OTH AF: 0.202

GnomAD4 exome AF: 0.236 AC: 253616 AN: 1072536 Hom.: 32514 Cov.: 14 AF XY: 0.237 AC XY: 128421 AN XY: 541920

Gnomad4 AFR exome AF: 0.0442

Gnomad4 AMR exome AF: 0.177

Gnomad4 ASJ exome AF: 0.169

Gnomad4 EAS exome AF: 0.492

Gnomad4 SAS exome AF: 0.207

Gnomad4 FIN exome AF: 0.238

Gnomad4 NFE exome AF: 0.239

Gnomad4 OTH exome AF: 0.228

GnomAD4 genome AF: 0.188 AC: 28587 AN: 152154 Hom.: 3448 Cov.: 32 AF XY: 0.189 AC XY: 14072 AN XY: 74368

Gnomad4 AFR AF: 0.0494

Gnomad4 AMR AF: 0.185

Gnomad4 ASJ AF: 0.164

Gnomad4 EAS AF: 0.466

Gnomad4 SAS AF: 0.203

Gnomad4 FIN AF: 0.242

Gnomad4 NFE AF: 0.244

Gnomad4 OTH AF: 0.204

Alfa AF: 0.219 Hom.: 6398

Bravo AF: 0.179

Asia WGS AF: 0.265 AC: 921 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.67
CADD	Benign	8.1
DANN	Benign	0.83

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

Publications

LitVar

Other links and lift over

dbSNP: rs3094; hg19: chr14-21168055; COSMIC: COSV59012141; COSMIC: COSV59012141;