chr11-67058689-C-T

Variant names:

• chr11-67058689-C-T
• rs7112925
• NM_014578.4:c.132+1655C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_014578.4(RHOD):​c.132+1655C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.358 in 151,882 control chromosomes in the GnomAD database, including 9,908 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 0.36 (9908 hom., cov: 32)
• Consequence: RHOD NM_014578.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.122
• Publications: 43 publications found

Genes affected

RHOD (HGNC:670): (ras homolog family member D) Ras homolog, or Rho, proteins interact with protein kinases and may serve as targets for activated GTPase. They play a critical role in muscle differentiation. The protein encoded by this gene binds GTP and is a member of the small GTPase superfamily. It is involved in endosome dynamics and reorganization of the actin cytoskeleton, and it may coordinate membrane transport with the function of the cytoskeleton. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2014]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.497 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RHOD	NM_014578.4	c.132+1655C>T		intron_variant	Intron 1 of 4	ENST00000308831.7	NP_055393.1
RHOD	NM_001300886.2	c.132+1655C>T		intron_variant	Intron 1 of 2		NP_001287815.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RHOD	ENST00000308831.7	c.132+1655C>T		intron_variant	Intron 1 of 4	1	NM_014578.4	ENSP00000308576.2
RHOD	ENST00000532559.1	c.132+1655C>T		intron_variant	Intron 1 of 2	3		ENSP00000432003.1
RHOD	ENST00000533360.2	n.175+1655C>T		intron_variant	Intron 1 of 3	2

Frequencies

GnomAD3 genomes AF: 0.358 AC: 54362 AN: 151762 Hom.: 9910 Cov.: 32

Gnomad AFR AF: 0.346

Gnomad AMI AF: 0.403

Gnomad AMR AF: 0.346

Gnomad ASJ AF: 0.419

Gnomad EAS AF: 0.463

Gnomad SAS AF: 0.514

Gnomad FIN AF: 0.276

Gnomad MID AF: 0.378

Gnomad NFE AF: 0.358

Gnomad OTH AF: 0.373

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.358 AC: 54384 AN: 151882 Hom.: 9908 Cov.: 32 AF XY: 0.358 AC XY: 26593 AN XY: 74248

African (AFR) AF: 0.346 AC: 14313 AN: 41386

American (AMR) AF: 0.346 AC: 5276 AN: 15254

Ashkenazi Jewish (ASJ) AF: 0.419 AC: 1453 AN: 3468

East Asian (EAS) AF: 0.464 AC: 2384 AN: 5140

South Asian (SAS) AF: 0.513 AC: 2476 AN: 4822

European-Finnish (FIN) AF: 0.276 AC: 2904 AN: 10536

Middle Eastern (MID) AF: 0.380 AC: 111 AN: 292

European-Non Finnish (NFE) AF: 0.358 AC: 24306 AN: 67964

Other (OTH) AF: 0.376 AC: 794 AN: 2110

Alfa AF: 0.360 Hom.: 42114

Bravo AF: 0.358

Asia WGS AF: 0.437 AC: 1522 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	5.0
DANN	Benign	0.35
PhyloP100		0.12
Mutation Taster		=100/0	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: rs7112925; hg19: chr11-66826160;