Variant chr11-535649-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

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

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.0840

Variant links:

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]

HRAS links:

LRRC56 (HGNC:):

LRRC56 links:

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ACMG classification

Classification made for transcript

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	Effect
LRRC56	XM_011519875.3 linkuse as main transcript	c.-424-2949C>T	intron_variant
LRRC56	XM_011519877.3 linkuse as main transcript	c.-161-3931C>T	intron_variant
LRRC56	XM_017017167.2 linkuse as main transcript	c.-499-2874C>T	intron_variant

Ensembl

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

Frequencies

GnomAD3 genomes

AF:

0.241

AC:

36626

AN:

151744

Hom.:

4822

Cov.:

show subpopulations

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:

AN:

Hom.:

AF XY:

0.350

AC XY:

AN XY:

show subpopulations

Gnomad4 NFE exome

AF:

0.273

Gnomad4 OTH exome

AF:

0.500

GnomAD4 genome

AF:

0.241

AC:

36662

AN:

151852

Hom.:

4833

Cov.:

AF XY:

0.240

AC XY:

17810

AN XY:

74224

show subpopulations

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

LINK: link

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

DANN

Benign

0.94

Splicing

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over