rs8176330

chr11-535798-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000468682.2(HRAS):c.-54+1055C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0957 in 152,160 control chromosomes in the GnomAD database, including 958 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 0.096 (958 hom., cov: 33)
• Consequence: HRAS ENST00000468682.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.269

Genes affected

HRAS (HGNC:5173): (HRas proto-oncogene, GTPase) This gene belongs to the Ras oncogene family, whose members are related to the transforming genes of mammalian sarcoma retroviruses. The products encoded by these genes function in signal transduction pathways. These proteins can bind GTP and GDP, and they have intrinsic GTPase activity. This protein undergoes a continuous cycle of de- and re-palmitoylation, which regulates its rapid exchange between the plasma membrane and the Golgi apparatus. Mutations in this gene cause Costello syndrome, a disease characterized by increased growth at the prenatal stage, growth deficiency at the postnatal stage, predisposition to tumor formation, cognitive disability, skin and musculoskeletal abnormalities, distinctive facial appearance and cardiovascular abnormalities. Defects in this gene are implicated in a variety of cancers, including bladder cancer, follicular thyroid cancer, and oral squamous cell carcinoma. Multiple transcript variants, which encode different isoforms, have been identified for this gene. [provided by RefSeq, Jul 2008]

LRRC56 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.74).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.182 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LRRC56	XM_011519875.3	c.-424-2800G>A		intron_variant
LRRC56	XM_011519877.3	c.-161-3782G>A		intron_variant
LRRC56	XM_017017167.2	c.-499-2725G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HRAS	ENST00000468682.2	c.-54+1055C>T		intron_variant		3
HRAS	ENST00000462734.2	c.-54+538C>T		intron_variant, NMD_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.0957 AC: 14548 AN: 152052 Hom.: 955 Cov.: 33

Gnomad AFR AF: 0.0261

Gnomad AMI AF: 0.0846

Gnomad AMR AF: 0.187

Gnomad ASJ AF: 0.101

Gnomad EAS AF: 0.00174

Gnomad SAS AF: 0.0366

Gnomad FIN AF: 0.0780

Gnomad MID AF: 0.0287

Gnomad NFE AF: 0.132

Gnomad OTH AF: 0.103

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

GnomAD4 genome AF: 0.0957 AC: 14555 AN: 152160 Hom.: 958 Cov.: 33 AF XY: 0.0934 AC XY: 6950 AN XY: 74374

Gnomad4 AFR AF: 0.0260

Gnomad4 AMR AF: 0.188

Gnomad4 ASJ AF: 0.101

Gnomad4 EAS AF: 0.00174

Gnomad4 SAS AF: 0.0369

Gnomad4 FIN AF: 0.0780

Gnomad4 NFE AF: 0.132

Gnomad4 OTH AF: 0.102

Alfa AF: 0.120 Hom.: 166

Bravo AF: 0.101

Asia WGS AF: 0.0310 AC: 106 AN: 3460

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.74
Cadd	Benign	5.6
Dann	Benign	0.76

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs8176330; hg19: chr11-535798;