rs8176331

Positions:

• chr11-535783-C-A
• chr11-535783-C-T

Variant summary

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

The ENST00000468682.2(HRAS):​c.-54+1070G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.24 in 151,792 control chromosomes in the GnomAD database, including 4,764 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 0.24 (4764 hom., cov: 33)
• Consequence: HRAS ENST00000468682.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.87

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=-0.7).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.335 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LRRC56	XM_011519875.3	c.-424-2815C>A		intron_variant			XP_011518177.1
LRRC56	XM_011519877.3	c.-161-3797C>A		intron_variant			XP_011518179.1
LRRC56	XM_017017167.2	c.-499-2740C>A		intron_variant			XP_016872656.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HRAS	ENST00000468682.2	c.-54+1070G>T		intron_variant		3		ENSP00000507989
HRAS	ENST00000462734.2	c.-54+553G>T		intron_variant, NMD_transcript_variant		2		ENSP00000507303

Frequencies

GnomAD3 genomes AF: 0.240 AC: 36365 AN: 151684 Hom.: 4753 Cov.: 33

Gnomad AFR AF: 0.340

Gnomad AMI AF: 0.267

Gnomad AMR AF: 0.184

Gnomad ASJ AF: 0.167

Gnomad EAS AF: 0.184

Gnomad SAS AF: 0.215

Gnomad FIN AF: 0.178

Gnomad MID AF: 0.245

Gnomad NFE AF: 0.211

Gnomad OTH AF: 0.227

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

GnomAD4 genome AF: 0.240 AC: 36401 AN: 151792 Hom.: 4764 Cov.: 33 AF XY: 0.238 AC XY: 17694 AN XY: 74198

Gnomad4 AFR AF: 0.340

Gnomad4 AMR AF: 0.184

Gnomad4 ASJ AF: 0.167

Gnomad4 EAS AF: 0.184

Gnomad4 SAS AF: 0.215

Gnomad4 FIN AF: 0.178

Gnomad4 NFE AF: 0.211

Gnomad4 OTH AF: 0.231

Alfa AF: 0.106 Hom.: 159

Bravo AF: 0.242

Asia WGS AF: 0.212 AC: 733 AN: 3464

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.70
CADD	Benign	5.7
DANN	Benign	0.50

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs8176331; hg19: chr11-535783;