NM_178861.5:c.315A>G

Variant names:

• chr13-98176922-T-C
• rs628778
• NM_178861.5:c.315A>G

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_178861.5(RNF113B):​c.315A>G​(p.Pro105Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.911 in 1,604,042 control chromosomes in the GnomAD database, including 676,470 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 0.78 (50659 hom., cov: 29)
  • Exomes 𝑓: 0.92 (625811 hom.)
• Consequence: RNF113B NM_178861.5 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.06
• Publications: 17 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: Benign. The variant received -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.7).
• BP7: Synonymous conserved (PhyloP=-3.06 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.935 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RNF113B	NM_178861.5	c.315A>G	p.Pro105Pro	synonymous_variant	Exon 1 of 2	ENST00000267291.7	NP_849192.1
FARP1	NM_005766.4	c.-24+33430T>C		intron_variant	Intron 1 of 26	ENST00000319562.11	NP_005757.1
FARP1	NM_001286839.2	c.-24+34145T>C		intron_variant	Intron 1 of 27		NP_001273768.1
FARP1	NM_001001715.4	c.-24+33430T>C		intron_variant	Intron 1 of 2		NP_001001715.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RNF113B	ENST00000267291.7	c.315A>G	p.Pro105Pro	synonymous_variant	Exon 1 of 2	1	NM_178861.5	ENSP00000267291.6
FARP1	ENST00000319562.11	c.-24+33430T>C		intron_variant	Intron 1 of 26	1	NM_005766.4	ENSP00000322926.6

Frequencies

GnomAD3 genomes AF: 0.783 AC: 118826 AN: 151690 Hom.: 50659 Cov.: 29

Gnomad AFR AF: 0.412

Gnomad AMI AF: 0.950

Gnomad AMR AF: 0.813

Gnomad ASJ AF: 0.950

Gnomad EAS AF: 0.934

Gnomad SAS AF: 0.919

Gnomad FIN AF: 0.962

Gnomad MID AF: 0.873

Gnomad NFE AF: 0.941

Gnomad OTH AF: 0.817

GnomAD2 exomes AF: 0.890 AC: 217872 AN: 244700 AF XY: 0.903

Gnomad AFR exome AF: 0.399

Gnomad AMR exome AF: 0.850

Gnomad ASJ exome AF: 0.941

Gnomad EAS exome AF: 0.945

Gnomad FIN exome AF: 0.958

Gnomad NFE exome AF: 0.940

Gnomad OTH exome AF: 0.913

GnomAD4 exome AF: 0.924 AC: 1342277 AN: 1452234 Hom.: 625811 Cov.: 88 AF XY: 0.926 AC XY: 669502 AN XY: 722862

African (AFR) AF: 0.396 AC: 13262 AN: 33476

American (AMR) AF: 0.849 AC: 37964 AN: 44712

Ashkenazi Jewish (ASJ) AF: 0.944 AC: 24669 AN: 26128

East Asian (EAS) AF: 0.911 AC: 36157 AN: 39696

South Asian (SAS) AF: 0.929 AC: 80095 AN: 86258

European-Finnish (FIN) AF: 0.959 AC: 42102 AN: 43924

Middle Eastern (MID) AF: 0.912 AC: 5257 AN: 5766

European-Non Finnish (NFE) AF: 0.943 AC: 1048146 AN: 1111942

Other (OTH) AF: 0.905 AC: 54625 AN: 60332

GnomAD4 genome AF: 0.783 AC: 118860 AN: 151808 Hom.: 50659 Cov.: 29 AF XY: 0.786 AC XY: 58329 AN XY: 74170

African (AFR) AF: 0.412 AC: 17033 AN: 41364

American (AMR) AF: 0.813 AC: 12411 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.950 AC: 3297 AN: 3470

East Asian (EAS) AF: 0.934 AC: 4761 AN: 5096

South Asian (SAS) AF: 0.919 AC: 4380 AN: 4766

European-Finnish (FIN) AF: 0.962 AC: 10187 AN: 10592

Middle Eastern (MID) AF: 0.866 AC: 253 AN: 292

European-Non Finnish (NFE) AF: 0.941 AC: 63949 AN: 67940

Other (OTH) AF: 0.817 AC: 1723 AN: 2110

Alfa AF: 0.900 Hom.: 188800

Bravo AF: 0.757

Asia WGS AF: 0.884 AC: 3075 AN: 3478

EpiCase AF: 0.939

EpiControl AF: 0.934

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.70
CADD	Benign	0.85
DANN	Benign	0.49
PhyloP100		-3.1
PromoterAI		0.027	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=98/2	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: rs628778; hg19: chr13-98829176; COSMIC: COSV108031914; COSMIC: COSV108031914;