rs8176333

chr11-535649-C-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The ENST00000468682.2(HRAS):c.-54+1204G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.241 in 151,876 control chromosomes in the GnomAD database, including 4,833 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.24 (4833 hom., cov: 33)
  • Exomes 𝑓: 0.29 (0 hom.)
• Consequence: HRAS ENST00000468682.2 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.0840

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.49).
• BP6: Variant 11-535649-C-T is Benign according to our data. Variant chr11-535649-C-T is described in ClinVar as [Benign]. Clinvar id is 1259531.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.337 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LRRC56	XM_011519875.3	c.-424-2949C>T		intron_variant
LRRC56	XM_011519877.3	c.-161-3931C>T		intron_variant
LRRC56	XM_017017167.2	c.-499-2874C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HRAS	ENST00000468682.2	c.-54+1204G>A		intron_variant		3
HRAS	ENST00000462734.2	c.-54+687G>A		intron_variant, NMD_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.241 AC: 36626 AN: 151744 Hom.: 4822 Cov.: 33

Gnomad AFR AF: 0.342

Gnomad AMI AF: 0.268

Gnomad AMR AF: 0.185

Gnomad ASJ AF: 0.168

Gnomad EAS AF: 0.186

Gnomad SAS AF: 0.215

Gnomad FIN AF: 0.179

Gnomad MID AF: 0.245

Gnomad NFE AF: 0.213

Gnomad OTH AF: 0.228

GnomAD4 exome AF: 0.292 AC: 7 AN: 24 Hom.: 0 AF XY: 0.350 AC XY: 7 AN XY: 20

Gnomad4 NFE exome AF: 0.273

Gnomad4 OTH exome AF: 0.500

GnomAD4 genome AF: 0.241 AC: 36662 AN: 151852 Hom.: 4833 Cov.: 33 AF XY: 0.240 AC XY: 17810 AN XY: 74224

Gnomad4 AFR AF: 0.342

Gnomad4 AMR AF: 0.184

Gnomad4 ASJ AF: 0.168

Gnomad4 EAS AF: 0.186

Gnomad4 SAS AF: 0.216

Gnomad4 FIN AF: 0.179

Gnomad4 NFE AF: 0.213

Gnomad4 OTH AF: 0.232

Alfa AF: 0.228 Hom.: 514

Bravo AF: 0.243

Asia WGS AF: 0.212 AC: 729 AN: 3448

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 23, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.49
Cadd	Benign	10
Dann	Benign	0.94

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs8176333; hg19: chr11-535649; COSMIC: COSV54238366;