rs2233859

Positions:

• chr14-20891649-C-A
• chr14-20891649-C-G
• chr14-20891649-C-T

Variant summary

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

The NM_002935.3(RNASE3):​c.-5-33C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.41 in 1,580,732 control chromosomes in the GnomAD database, including 139,827 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 0.34 (10696 hom., cov: 30)
  • Exomes 𝑓: 0.42 (129131 hom.)
• Consequence: RNASE3 NM_002935.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.847

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=-0.9).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.478 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RNASE3	NM_002935.3	c.-5-33C>A		intron_variant		ENST00000304639.4	NP_002926.2
LOC100507513	XR_110261.4	n.723-15906G>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RNASE3	ENST00000304639.4	c.-5-33C>A		intron_variant		1	NM_002935.3	ENSP00000302324	P1

Frequencies

GnomAD3 genomes AF: 0.338 AC: 50931 AN: 150502 Hom.: 10690 Cov.: 30

Gnomad AFR AF: 0.0952

Gnomad AMI AF: 0.381

Gnomad AMR AF: 0.487

Gnomad ASJ AF: 0.346

Gnomad EAS AF: 0.273

Gnomad SAS AF: 0.408

Gnomad FIN AF: 0.499

Gnomad MID AF: 0.369

Gnomad NFE AF: 0.423

Gnomad OTH AF: 0.342

GnomAD3 exomes AF: 0.415 AC: 93551 AN: 225212 Hom.: 21358 AF XY: 0.418 AC XY: 50491 AN XY: 120800

Gnomad AFR exome AF: 0.0899

Gnomad AMR exome AF: 0.585

Gnomad ASJ exome AF: 0.350

Gnomad EAS exome AF: 0.293

Gnomad SAS exome AF: 0.411

Gnomad FIN exome AF: 0.503

Gnomad NFE exome AF: 0.424

Gnomad OTH exome AF: 0.417

GnomAD4 exome AF: 0.418 AC: 597643 AN: 1430116 Hom.: 129131 Cov.: 38 AF XY: 0.418 AC XY: 295963 AN XY: 708800

Gnomad4 AFR exome AF: 0.0816

Gnomad4 AMR exome AF: 0.573

Gnomad4 ASJ exome AF: 0.349

Gnomad4 EAS exome AF: 0.254

Gnomad4 SAS exome AF: 0.420

Gnomad4 FIN exome AF: 0.498

Gnomad4 NFE exome AF: 0.426

Gnomad4 OTH exome AF: 0.401

GnomAD4 genome AF: 0.338 AC: 50949 AN: 150616 Hom.: 10696 Cov.: 30 AF XY: 0.346 AC XY: 25443 AN XY: 73574

Gnomad4 AFR AF: 0.0949

Gnomad4 AMR AF: 0.487

Gnomad4 ASJ AF: 0.346

Gnomad4 EAS AF: 0.273

Gnomad4 SAS AF: 0.409

Gnomad4 FIN AF: 0.499

Gnomad4 NFE AF: 0.423

Gnomad4 OTH AF: 0.342

Alfa AF: 0.385 Hom.: 12035

Bravo AF: 0.326

Asia WGS AF: 0.323 AC: 1123 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.42
DANN	Benign	0.52

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

Publications

LitVar

Other links and lift over

dbSNP: rs2233859; hg19: chr14-21359808; COSMIC: COSV58959824;