14-20892185-G-C

Variant names:

• chr14-20892185-G-C
• rs2233860
• NM_002935.3:c.*16G>C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 22 publications found

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]

ENSG00000259130 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002935.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RNASE3	NM_002935.3	MANE Select	c.*16G>C		3_prime_UTR	Exon 2 of 2	NP_002926.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RNASE3	ENST00000304639.4	TSL:1 MANE Select	c.*16G>C		3_prime_UTR	Exon 2 of 2	ENSP00000302324.3
	ENSG00000259130	ENST00000717679.1		n.259-16442C>G		intron	N/A
	ENSG00000259130	ENST00000717680.1		n.347-16442C>G		intron	N/A

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

GnomAD2 exomes AF: 0.177 AC: 41617 AN: 235548 AF XY: 0.180

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 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

African (AFR) AF: 0.220 AC: 7222 AN: 32764

American (AMR) AF: 0.101 AC: 4357 AN: 43068

Ashkenazi Jewish (ASJ) AF: 0.215 AC: 5264 AN: 24510

East Asian (EAS) AF: 0.146 AC: 5781 AN: 39622

South Asian (SAS) AF: 0.161 AC: 13328 AN: 82828

European-Finnish (FIN) AF: 0.151 AC: 7911 AN: 52470

Middle Eastern (MID) AF: 0.208 AC: 1176 AN: 5652

European-Non Finnish (NFE) AF: 0.200 AC: 220485 AN: 1103608

Other (OTH) AF: 0.187 AC: 11123 AN: 59614

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

African (AFR) AF: 0.219 AC: 8800 AN: 40132

American (AMR) AF: 0.149 AC: 2270 AN: 15226

Ashkenazi Jewish (ASJ) AF: 0.208 AC: 721 AN: 3470

East Asian (EAS) AF: 0.134 AC: 690 AN: 5160

South Asian (SAS) AF: 0.154 AC: 739 AN: 4810

European-Finnish (FIN) AF: 0.151 AC: 1590 AN: 10552

Middle Eastern (MID) AF: 0.195 AC: 57 AN: 292

European-Non Finnish (NFE) AF: 0.195 AC: 13275 AN: 67964

Other (OTH) AF: 0.191 AC: 402 AN: 2104

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	1.4
DANN	Benign	0.37
PhyloP100		-0.11
Mutation Taster		=100/0	polymorphism (auto)

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