chr11-535777-G-T

Position:

• chr11-535777-G-T

Variant summary

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

The ENST00000468682.2(HRAS):​c.-54+1076C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.14 in 151,944 control chromosomes in the GnomAD database, including 2,087 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 0.14 (2087 hom., cov: 33)
• Consequence: HRAS ENST00000468682.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.238

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:25430): (leucine rich repeat containing 56) Predicted to be involved in cell projection organization. Predicted to be located in cilium. Implicated in primary ciliary dyskinesia 39. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.76).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.276 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LRRC56	XM_011519875.3	c.-424-2821G>T		intron_variant			XP_011518177.1
LRRC56	XM_011519877.3	c.-161-3803G>T		intron_variant			XP_011518179.1
LRRC56	XM_017017167.2	c.-499-2746G>T		intron_variant			XP_016872656.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HRAS	ENST00000468682.2	c.-54+1076C>A		intron_variant		3		ENSP00000507989.1
HRAS	ENST00000462734.2	n.-54+559C>A		intron_variant		2		ENSP00000507303.1

Frequencies

GnomAD3 genomes AF: 0.140 AC: 21307 AN: 151836 Hom.: 2084 Cov.: 33

Gnomad AFR AF: 0.280

Gnomad AMI AF: 0.0473

Gnomad AMR AF: 0.106

Gnomad ASJ AF: 0.0790

Gnomad EAS AF: 0.0544

Gnomad SAS AF: 0.0280

Gnomad FIN AF: 0.0610

Gnomad MID AF: 0.140

Gnomad NFE AF: 0.0942

Gnomad OTH AF: 0.137

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

GnomAD4 genome AF: 0.140 AC: 21329 AN: 151944 Hom.: 2087 Cov.: 33 AF XY: 0.137 AC XY: 10152 AN XY: 74270

Gnomad4 AFR AF: 0.280

Gnomad4 AMR AF: 0.106

Gnomad4 ASJ AF: 0.0790

Gnomad4 EAS AF: 0.0545

Gnomad4 SAS AF: 0.0280

Gnomad4 FIN AF: 0.0610

Gnomad4 NFE AF: 0.0942

Gnomad4 OTH AF: 0.136

Alfa AF: 0.0265 Hom.: 21

Bravo AF: 0.150

Asia WGS AF: 0.0560 AC: 194 AN: 3464

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.76
CADD	Benign	4.7
DANN	Benign	0.49

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs8176332; hg19: chr11-535777;