chr13-98176674-C-T

Variant names:

• chr13-98176674-C-T
• rs140282190
• NM_178861.5:c.563G>A

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_178861.5(RNF113B):​c.563G>A​(p.Arg188His) variant causes a missense change. The variant allele was found at a frequency of 0.0000551 in 1,614,228 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.00026 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000034 (0 hom.)
• Consequence: RNF113B NM_178861.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.07
• Publications: 0 publications found

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]

ACMG classification

Our verdict: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.06384018).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_178861.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RNF113B	NM_178861.5	MANE Select	c.563G>A	p.Arg188His	missense	Exon 1 of 2	NP_849192.1	Q8IZP6
	FARP1	NM_005766.4	MANE Select	c.-24+33182C>T		intron	N/A	NP_005757.1	A0A2X0TVY0
	FARP1	NM_001286839.2		c.-24+33897C>T		intron	N/A	NP_001273768.1	C9JME2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RNF113B	ENST00000267291.7	TSL:1 MANE Select	c.563G>A	p.Arg188His	missense	Exon 1 of 2	ENSP00000267291.6	Q8IZP6
	FARP1	ENST00000319562.11	TSL:1 MANE Select	c.-24+33182C>T		intron	N/A	ENSP00000322926.6	Q9Y4F1-1
	FARP1	ENST00000595437.5	TSL:1	c.-24+33897C>T		intron	N/A	ENSP00000471242.1	C9JME2

Frequencies

GnomAD3 genomes AF: 0.000256 AC: 39 AN: 152216 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000917

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000654

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000875 AC: 22 AN: 251444 AF XY: 0.0000736

Gnomad AFR exome AF: 0.000984

Gnomad AMR exome AF: 0.000145

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000342 AC: 50 AN: 1461894 Hom.: 0 Cov.: 32 AF XY: 0.0000303 AC XY: 22 AN XY: 727248

African (AFR) AF: 0.00111 AC: 37 AN: 33480

American (AMR) AF: 0.000157 AC: 7 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.0000232 AC: 2 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53420

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 8.99e-7 AC: 1 AN: 1112012

Other (OTH) AF: 0.0000497 AC: 3 AN: 60396

GnomAD4 genome AF: 0.000256 AC: 39 AN: 152334 Hom.: 0 Cov.: 32 AF XY: 0.000242 AC XY: 18 AN XY: 74482

African (AFR) AF: 0.000914 AC: 38 AN: 41584

American (AMR) AF: 0.0000654 AC: 1 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5178

South Asian (SAS) AF: 0.00 AC: 0 AN: 4830

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10620

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68026

Other (OTH) AF: 0.00 AC: 0 AN: 2116

Alfa AF: 0.000197 Hom.: 0

Bravo AF: 0.000280

ESP6500AA AF: 0.000908 AC: 4

ESP6500EA AF: 0.00 AC: 0

ExAC AF: 0.0000906 AC: 11

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.17
BayesDel_addAF	Benign	-0.39	T
BayesDel_noAF	Benign	-0.39
CADD	Uncertain	24
DANN	Uncertain	0.99
DEOGEN2	Benign	0.29	T
Eigen	Benign	-0.30
Eigen_PC	Benign	-0.37
FATHMM_MKL	Benign	0.53	D
LIST_S2	Uncertain	0.94	D
M_CAP	Benign	0.0067	T
MetaRNN	Benign	0.064	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.5	M
PhyloP100		4.1
PrimateAI	Benign	0.42	T
PROVEAN	Pathogenic	-5.0	D
REVEL	Benign	0.13
Sift	Uncertain	0.0010	D
Sift4G	Uncertain	0.017	D
Polyphen		0.54	P
Vest4		0.32
MVP		0.52
MPC		0.78
ClinPred		0.20	T
GERP RS		0.27
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.43
gMVP		0.80
Mutation Taster		=77/23	polymorphism

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: rs140282190; hg19: chr13-98828928;