rs8176334

chr11-535603-G-Achr11-535603-G-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Moderate BP6_Moderate BA1

The ENST00000468682.2(HRAS):c.-53-1228C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0623 in 151,302 control chromosomes in the GnomAD database, including 349 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.062 (349 hom., cov: 33)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: HRAS ENST00000468682.2 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.606

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=-0.31).
• BP6: Variant 11-535603-G-A is Benign according to our data. Variant chr11-535603-G-A is described in ClinVar as [Benign]. Clinvar id is 1279995.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0896 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
HRAS	NM_005343.4			upstream_gene_variant		ENST00000311189.8
HRAS	NM_176795.5			upstream_gene_variant		ENST00000417302.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HRAS	ENST00000468682.2	c.-53-1228C>T		intron_variant		3
HRAS	ENST00000462734.2	c.-54+733C>T		intron_variant, NMD_transcript_variant		2
HRAS	ENST00000311189.8			upstream_gene_variant		1	NM_005343.4	P1
HRAS	ENST00000417302.7			upstream_gene_variant		5	NM_176795.5

Frequencies

GnomAD3 genomes AF: 0.0624 AC: 9428 AN: 151194 Hom.: 350 Cov.: 33

Gnomad AFR AF: 0.0165

Gnomad AMI AF: 0.0474

Gnomad AMR AF: 0.0710

Gnomad ASJ AF: 0.0761

Gnomad EAS AF: 0.0481

Gnomad SAS AF: 0.0209

Gnomad FIN AF: 0.0587

Gnomad MID AF: 0.115

Gnomad NFE AF: 0.0916

Gnomad OTH AF: 0.0848

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 8 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 6

Gnomad4 NFE exome AF: 0.00

GnomAD4 genome AF: 0.0623 AC: 9424 AN: 151302 Hom.: 349 Cov.: 33 AF XY: 0.0611 AC XY: 4519 AN XY: 73944

Gnomad4 AFR AF: 0.0165

Gnomad4 AMR AF: 0.0709

Gnomad4 ASJ AF: 0.0761

Gnomad4 EAS AF: 0.0482

Gnomad4 SAS AF: 0.0209

Gnomad4 FIN AF: 0.0587

Gnomad4 NFE AF: 0.0915

Gnomad4 OTH AF: 0.0839

Alfa AF: 0.0314 Hom.: 24

Bravo AF: 0.0604

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	-0.31
Cadd	Benign	16
Dann	Benign	0.97

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs8176334; hg19: chr11-535603;