rs16955011

Positions:

• chr13-98176963-C-T

Variant summary

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

The NM_178861.5(RNF113B):​c.274G>A​(p.Val92Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0658 in 1,600,954 control chromosomes in the GnomAD database, including 4,323 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

• Frequency:
  • Genomes: 𝑓 0.095 (928 hom., cov: 31)
  • Exomes 𝑓: 0.063 (3395 hom.)
• Consequence: RNF113B NM_178861.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.952

Genes affected

RNF113B (HGNC:17267): (ring finger protein 113B) Predicted to enable metal ion binding activity. Predicted to be involved in snoRNA splicing. Predicted to be part of U2-type spliceosomal complex. [provided by Alliance of Genome Resources, Apr 2022]

FARP1 (HGNC:3591): (FERM, ARH/RhoGEF and pleckstrin domain protein 1) This gene encodes a protein containing a FERM (4.2, exrin, radixin, moesin) domain, a Dbl homology domain, and two pleckstrin homology domains. These domains are found in guanine nucleotide exchange factors and proteins that link the cytoskeleton to the cell membrane. The encoded protein functions in neurons to promote dendritic growth. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Nov 2013]

FARP1 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0012420118).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.167 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RNF113B	NM_178861.5	c.274G>A	p.Val92Met	missense_variant	1/2	ENST00000267291.7	NP_849192.1
FARP1	NM_005766.4	c.-24+33471C>T		intron_variant		ENST00000319562.11	NP_005757.1
FARP1	NM_001286839.2	c.-24+34186C>T		intron_variant			NP_001273768.1
FARP1	NM_001001715.4	c.-24+33471C>T		intron_variant			NP_001001715.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RNF113B	ENST00000267291.7	c.274G>A	p.Val92Met	missense_variant	1/2	1	NM_178861.5	ENSP00000267291.6
FARP1	ENST00000319562.11	c.-24+33471C>T		intron_variant		1	NM_005766.4	ENSP00000322926.6

Frequencies

GnomAD3 genomes AF: 0.0953 AC: 14474 AN: 151856 Hom.: 924 Cov.: 31

Gnomad AFR AF: 0.170

Gnomad AMI AF: 0.0505

Gnomad AMR AF: 0.135

Gnomad ASJ AF: 0.0438

Gnomad EAS AF: 0.0641

Gnomad SAS AF: 0.0770

Gnomad FIN AF: 0.0380

Gnomad MID AF: 0.0701

Gnomad NFE AF: 0.0570

Gnomad OTH AF: 0.0898

GnomAD3 exomes AF: 0.0766 AC: 18337 AN: 239378 Hom.: 899 AF XY: 0.0724 AC XY: 9430 AN XY: 130318

Gnomad AFR exome AF: 0.171

Gnomad AMR exome AF: 0.126

Gnomad ASJ exome AF: 0.0506

Gnomad EAS exome AF: 0.0552

Gnomad SAS exome AF: 0.0737

Gnomad FIN exome AF: 0.0432

Gnomad NFE exome AF: 0.0585

Gnomad OTH exome AF: 0.0684

GnomAD4 exome AF: 0.0627 AC: 90787 AN: 1448980 Hom.: 3395 Cov.: 35 AF XY: 0.0623 AC XY: 44944 AN XY: 721292

Gnomad4 AFR exome AF: 0.172

Gnomad4 AMR exome AF: 0.125

Gnomad4 ASJ exome AF: 0.0467

Gnomad4 EAS exome AF: 0.0892

Gnomad4 SAS exome AF: 0.0700

Gnomad4 FIN exome AF: 0.0413

Gnomad4 NFE exome AF: 0.0565

Gnomad4 OTH exome AF: 0.0642

GnomAD4 genome AF: 0.0954 AC: 14502 AN: 151974 Hom.: 928 Cov.: 31 AF XY: 0.0960 AC XY: 7131 AN XY: 74292

Gnomad4 AFR AF: 0.170

Gnomad4 AMR AF: 0.135

Gnomad4 ASJ AF: 0.0438

Gnomad4 EAS AF: 0.0643

Gnomad4 SAS AF: 0.0768

Gnomad4 FIN AF: 0.0380

Gnomad4 NFE AF: 0.0570

Gnomad4 OTH AF: 0.0913

Alfa AF: 0.0663 Hom.: 730

Bravo AF: 0.106

TwinsUK AF: 0.0588 AC: 218

ALSPAC AF: 0.0592 AC: 228

ESP6500AA AF: 0.160 AC: 703

ESP6500EA AF: 0.0578 AC: 497

ExAC AF: 0.0744 AC: 9026

Asia WGS AF: 0.0840 AC: 290 AN: 3478

EpiCase AF: 0.0590

EpiControl AF: 0.0636

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.14
BayesDel_addAF	Benign	-0.72	T
BayesDel_noAF	Benign	-0.66
CADD	Benign	16
DANN	Benign	0.97
DEOGEN2	Benign	0.21	T
Eigen	Benign	-0.79
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.0044	N
LIST_S2	Benign	0.75	T
MetaRNN	Benign	0.0012	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Pathogenic	3.1	M
PrimateAI	Benign	0.45	T
PROVEAN	Uncertain	-2.4	N
REVEL	Benign	0.15
Sift	Uncertain	0.0030	D
Sift4G	Uncertain	0.014	D
Polyphen		0.98	D
Vest4		0.018
MPC		0.51
ClinPred		0.055	T
GERP RS		0.21
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.13
gMVP		0.73

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: rs16955011; hg19: chr13-98829217; COSMIC: COSV57434265; COSMIC: COSV57434265;