NM_001664.4:c.157-114C>T

Variant names:

• chr3-49368662-G-A
• rs11716445
• NM_001664.4:c.157-114C>T

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BA1

The NM_001664.4(RHOA):​c.157-114C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0725 in 1,080,842 control chromosomes in the GnomAD database, including 3,510 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 0.061 (401 hom., cov: 31)
  • Exomes 𝑓: 0.074 (3109 hom.)
• Consequence: RHOA NM_001664.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.205

Genes affected

RHOA (HGNC:667): (ras homolog family member A) This gene encodes a member of the Rho family of small GTPases, which cycle between inactive GDP-bound and active GTP-bound states and function as molecular switches in signal transduction cascades. Rho proteins promote reorganization of the actin cytoskeleton and regulate cell shape, attachment, and motility. Overexpression of this gene is associated with tumor cell proliferation and metastasis. Multiple alternatively spliced variants have been identified. [provided by RefSeq, Sep 2015]

ENSG00000290318 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -8 ACMG points.

• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.087 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RHOA	NM_001664.4	c.157-114C>T		intron_variant	Intron 2 of 4	ENST00000418115.6	NP_001655.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RHOA	ENST00000418115.6	c.157-114C>T		intron_variant	Intron 2 of 4	1	NM_001664.4	ENSP00000400175.1
ENSG00000290318	ENST00000704381.1	c.157-114C>T		intron_variant	Intron 2 of 5			ENSP00000515884.1

Frequencies

GnomAD3 genomes AF: 0.0606 AC: 9175 AN: 151398 Hom.: 401 Cov.: 31

Gnomad AFR AF: 0.0169

Gnomad AMI AF: 0.0872

Gnomad AMR AF: 0.0527

Gnomad ASJ AF: 0.0896

Gnomad EAS AF: 0.000385

Gnomad SAS AF: 0.0244

Gnomad FIN AF: 0.0953

Gnomad MID AF: 0.0669

Gnomad NFE AF: 0.0889

Gnomad OTH AF: 0.0589

GnomAD4 exome AF: 0.0745 AC: 69194 AN: 929342 Hom.: 3109 AF XY: 0.0731 AC XY: 34955 AN XY: 478010

Gnomad4 AFR exome AF: 0.0138

Gnomad4 AMR exome AF: 0.0419

Gnomad4 ASJ exome AF: 0.0853

Gnomad4 EAS exome AF: 0.000110

Gnomad4 SAS exome AF: 0.0219

Gnomad4 FIN exome AF: 0.0943

Gnomad4 NFE exome AF: 0.0862

Gnomad4 OTH exome AF: 0.0686

GnomAD4 genome AF: 0.0605 AC: 9171 AN: 151500 Hom.: 401 Cov.: 31 AF XY: 0.0601 AC XY: 4445 AN XY: 73998

Gnomad4 AFR AF: 0.0169

Gnomad4 AMR AF: 0.0527

Gnomad4 ASJ AF: 0.0896

Gnomad4 EAS AF: 0.000386

Gnomad4 SAS AF: 0.0240

Gnomad4 FIN AF: 0.0953

Gnomad4 NFE AF: 0.0889

Gnomad4 OTH AF: 0.0578

Alfa AF: 0.0716 Hom.: 254

Bravo AF: 0.0558

Asia WGS AF: 0.0100 AC: 38 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	19
DANN	Benign	0.78

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.32		Details are displayed if max score is > 0.2
DS_AG_spliceai		0.32		Position offset: 1
DS_DG_spliceai		0.27		Position offset: -40

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs11716445; hg19: chr3-49406095;