12-48862015-G-C

Position:

• chr12-48862015-G-C

Variant summary

Our verdict is Benign. Variant got -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

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]

RND1 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RND1	NM_014470.4	c.312C>G	p.Leu104Leu	synonymous_variant	3/5	ENST00000309739.6	NP_055285.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RND1	ENST00000309739.6	c.312C>G	p.Leu104Leu	synonymous_variant	3/5	1	NM_014470.4	ENSP00000308461.5

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

GnomAD3 exomes AF: 0.466 AC: 116632 AN: 250288 Hom.: 27859 AF XY: 0.462 AC XY: 62516 AN XY: 135308

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 SAS exome AF: 0.434

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

Gnomad4 AFR exome AF: 0.331

Gnomad4 AMR exome AF: 0.596

Gnomad4 ASJ exome AF: 0.505

Gnomad4 EAS exome AF: 0.426

Gnomad4 SAS exome AF: 0.432

Gnomad4 FIN exome AF: 0.406

Gnomad4 NFE exome AF: 0.461

Gnomad4 OTH exome AF: 0.458

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

Gnomad4 AFR AF: 0.340

Gnomad4 AMR AF: 0.538

Gnomad4 ASJ AF: 0.524

Gnomad4 EAS AF: 0.407

Gnomad4 SAS AF: 0.426

Gnomad4 FIN AF: 0.400

Gnomad4 NFE AF: 0.460

Gnomad4 OTH AF: 0.460

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 v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.47
CADD	Benign	8.7
DANN	Benign	0.67

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

Publications

LitVar

Other links and lift over

dbSNP: rs1565933; hg19: chr12-49255798;