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. The variant received -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
• Publications: 23 publications found

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]

RHOA Gene-Disease associations (from GenCC):

• ectodermal dysplasia with facial dysmorphism and acral, ocular, and brain anomalies

  Inheritance: Unknown Classification: LIMITED Submitted by: Ambry Genetics

ENSG00000290318 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -8 ACMG points.

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001664.4. 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
	RHOA	NM_001664.4	MANE Select	c.157-114C>T		intron	N/A	NP_001655.1
	RHOA	NM_001313941.2		c.157-114C>T		intron	N/A	NP_001300870.1
	RHOA	NM_001313943.2		c.157-114C>T		intron	N/A	NP_001300872.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RHOA	ENST00000418115.6	TSL:1 MANE Select	c.157-114C>T		intron	N/A	ENSP00000400175.1
	ENSG00000290318	ENST00000704381.1		c.157-114C>T		intron	N/A	ENSP00000515884.1
	RHOA	ENST00000880080.1		c.158C>T	p.Thr53Ile	missense splice_region	Exon 3 of 6	ENSP00000550139.1

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

African (AFR) AF: 0.0138 AC: 295 AN: 21386

American (AMR) AF: 0.0419 AC: 1242 AN: 29618

Ashkenazi Jewish (ASJ) AF: 0.0853 AC: 1718 AN: 20138

East Asian (EAS) AF: 0.000110 AC: 4 AN: 36456

South Asian (SAS) AF: 0.0219 AC: 1483 AN: 67632

European-Finnish (FIN) AF: 0.0943 AC: 4732 AN: 50156

Middle Eastern (MID) AF: 0.0383 AC: 175 AN: 4570

European-Non Finnish (NFE) AF: 0.0862 AC: 56656 AN: 657298

Other (OTH) AF: 0.0686 AC: 2889 AN: 42088

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

African (AFR) AF: 0.0169 AC: 697 AN: 41316

American (AMR) AF: 0.0527 AC: 800 AN: 15178

Ashkenazi Jewish (ASJ) AF: 0.0896 AC: 311 AN: 3470

East Asian (EAS) AF: 0.000386 AC: 2 AN: 5180

South Asian (SAS) AF: 0.0240 AC: 115 AN: 4794

European-Finnish (FIN) AF: 0.0953 AC: 993 AN: 10416

Middle Eastern (MID) AF: 0.0719 AC: 21 AN: 292

European-Non Finnish (NFE) AF: 0.0889 AC: 6032 AN: 67854

Other (OTH) AF: 0.0578 AC: 121 AN: 2094

Alfa AF: 0.0748 Hom.: 942

Bravo AF: 0.0558

Asia WGS AF: 0.0100 AC: 38 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	19
DANN	Benign	0.78
PhyloP100		-0.20
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs11716445; hg19: chr3-49406095;