12-48862015-G-C

Variant names:

• chr12-48862015-G-C
• rs1565933
• NM_014470.4:c.312C>G

Variant summary

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

The NM_014470.4(RND1):​c.312C>G​(p.Leu104Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.455 in 1,569,074 control chromosomes in the GnomAD database, including 165,235 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 0.43 (14480 hom., cov: 32)
  • Exomes 𝑓: 0.46 (150755 hom.)
• Consequence: RND1 NM_014470.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.186
• Publications: 22 publications found

Genes affected

RND1 (HGNC:18314): (Rho family GTPase 1) This gene encodes a protein that belongs to the Rho GTPase family. Members of this family regulate the organization of the actin cytoskeleton in response to extracellular growth factors. A similar protein in rat interacts with a microtubule regulator to control axon extension. [provided by RefSeq, Apr 2014]

ACMG classification

Our verdict: Benign. The variant received -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.47).
• BP7: Synonymous conserved (PhyloP=-0.186 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.528 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014470.4. 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
	RND1	NM_014470.4	MANE Select	c.312C>G	p.Leu104Leu	synonymous	Exon 3 of 5	NP_055285.1	Q92730

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RND1	ENST00000309739.6	TSL:1 MANE Select	c.312C>G	p.Leu104Leu	synonymous	Exon 3 of 5	ENSP00000308461.5	Q92730
	RND1	ENST00000551243.1	TSL:3	n.*306C>G		non_coding_transcript_exon	Exon 3 of 4	ENSP00000449045.1	F8VXU4
	RND1	ENST00000553260.1	TSL:2	n.196C>G		non_coding_transcript_exon	Exon 1 of 3

Frequencies

GnomAD3 genomes AF: 0.430 AC: 65325 AN: 151962 Hom.: 14469 Cov.: 32

Gnomad AFR AF: 0.340

Gnomad AMI AF: 0.518

Gnomad AMR AF: 0.537

Gnomad ASJ AF: 0.524

Gnomad EAS AF: 0.408

Gnomad SAS AF: 0.427

Gnomad FIN AF: 0.400

Gnomad MID AF: 0.519

Gnomad NFE AF: 0.460

Gnomad OTH AF: 0.457

GnomAD2 exomes AF: 0.466 AC: 116632 AN: 250288 AF XY: 0.462

Gnomad AFR exome AF: 0.328

Gnomad AMR exome AF: 0.607

Gnomad ASJ exome AF: 0.513

Gnomad EAS exome AF: 0.409

Gnomad FIN exome AF: 0.402

Gnomad NFE exome AF: 0.468

Gnomad OTH exome AF: 0.484

GnomAD4 exome AF: 0.458 AC: 649279 AN: 1416994 Hom.: 150755 Cov.: 25 AF XY: 0.458 AC XY: 323965 AN XY: 707690

African (AFR) AF: 0.331 AC: 10828 AN: 32668

American (AMR) AF: 0.596 AC: 26545 AN: 44502

Ashkenazi Jewish (ASJ) AF: 0.505 AC: 13010 AN: 25772

East Asian (EAS) AF: 0.426 AC: 16809 AN: 39488

South Asian (SAS) AF: 0.432 AC: 36870 AN: 85286

European-Finnish (FIN) AF: 0.406 AC: 21641 AN: 53368

Middle Eastern (MID) AF: 0.531 AC: 3016 AN: 5678

European-Non Finnish (NFE) AF: 0.461 AC: 493549 AN: 1071320

Other (OTH) AF: 0.458 AC: 27011 AN: 58912

GnomAD4 genome AF: 0.430 AC: 65378 AN: 152080 Hom.: 14480 Cov.: 32 AF XY: 0.430 AC XY: 31985 AN XY: 74348

African (AFR) AF: 0.340 AC: 14117 AN: 41490

American (AMR) AF: 0.538 AC: 8220 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.524 AC: 1819 AN: 3472

East Asian (EAS) AF: 0.407 AC: 2110 AN: 5178

South Asian (SAS) AF: 0.426 AC: 2055 AN: 4820

European-Finnish (FIN) AF: 0.400 AC: 4227 AN: 10568

Middle Eastern (MID) AF: 0.520 AC: 153 AN: 294

European-Non Finnish (NFE) AF: 0.460 AC: 31233 AN: 67952

Other (OTH) AF: 0.460 AC: 972 AN: 2112

Alfa AF: 0.456 Hom.: 5322

Bravo AF: 0.444

Asia WGS AF: 0.462 AC: 1602 AN: 3478

EpiCase AF: 0.479

EpiControl AF: 0.485

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.47
CADD	Benign	8.7
DANN	Benign	0.67
PhyloP100		-0.19
Mutation Taster		=89/11	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: rs1565933; hg19: chr12-49255798; COSMIC: COSV100552117; COSMIC: COSV100552117;