rs2233860

Positions:

• chr14-20892185-G-C

Variant summary

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

The NM_002935.3(RNASE3):​c.*16G>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 0.192 in 1,594,758 control chromosomes in the GnomAD database, including 31,128 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 (3286 hom., cov: 30)
  • Exomes 𝑓: 0.19 (27842 hom.)
• Consequence: RNASE3 NM_002935.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.110

Genes affected

RNASE3 (HGNC:10046): (ribonuclease A family member 3) The protein encoded by this gene belongs to the pancreatic ribonuclease family, a subset of the ribonuclease A superfamily. The protein exhibits antimicrobial activity against pathogenic bacteria [provided by RefSeq, Oct 2014]

LOC100507513 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.99).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.215 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RNASE3	NM_002935.3	c.*16G>C		3_prime_UTR_variant	2/2	ENST00000304639.4
LOC100507513	XR_110261.4	n.723-16442C>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RNASE3	ENST00000304639.4	c.*16G>C		3_prime_UTR_variant	2/2	1	NM_002935.3	P1

Frequencies

GnomAD3 genomes AF: 0.191 AC: 28803 AN: 150504 Hom.: 3281 Cov.: 30

Gnomad AFR AF: 0.220

Gnomad AMI AF: 0.302

Gnomad AMR AF: 0.149

Gnomad ASJ AF: 0.208

Gnomad EAS AF: 0.134

Gnomad SAS AF: 0.154

Gnomad FIN AF: 0.151

Gnomad MID AF: 0.194

Gnomad NFE AF: 0.195

Gnomad OTH AF: 0.190

GnomAD3 exomes AF: 0.177 AC: 41617 AN: 235548 Hom.: 4239 AF XY: 0.180 AC XY: 22740 AN XY: 126594

Gnomad AFR exome AF: 0.226

Gnomad AMR exome AF: 0.0958

Gnomad ASJ exome AF: 0.223

Gnomad EAS exome AF: 0.144

Gnomad SAS exome AF: 0.170

Gnomad FIN exome AF: 0.150

Gnomad NFE exome AF: 0.202

Gnomad OTH exome AF: 0.187

GnomAD4 exome AF: 0.192 AC: 276647 AN: 1444136 Hom.: 27842 Cov.: 35 AF XY: 0.191 AC XY: 136947 AN XY: 716930

Gnomad4 AFR exome AF: 0.220

Gnomad4 AMR exome AF: 0.101

Gnomad4 ASJ exome AF: 0.215

Gnomad4 EAS exome AF: 0.146

Gnomad4 SAS exome AF: 0.161

Gnomad4 FIN exome AF: 0.151

Gnomad4 NFE exome AF: 0.200

Gnomad4 OTH exome AF: 0.187

GnomAD4 genome AF: 0.191 AC: 28819 AN: 150622 Hom.: 3286 Cov.: 30 AF XY: 0.189 AC XY: 13938 AN XY: 73622

Gnomad4 AFR AF: 0.219

Gnomad4 AMR AF: 0.149

Gnomad4 ASJ AF: 0.208

Gnomad4 EAS AF: 0.134

Gnomad4 SAS AF: 0.154

Gnomad4 FIN AF: 0.151

Gnomad4 NFE AF: 0.195

Gnomad4 OTH AF: 0.191

Alfa AF: 0.191 Hom.: 601

Bravo AF: 0.195

Asia WGS AF: 0.130 AC: 453 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	1.4
DANN	Benign	0.37

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: rs2233860; hg19: chr14-21360344; COSMIC: COSV58959257;