rs8176333

Positions:

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

2

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]

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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 HGVSp Effect #exon/exons MANE UniProt
LRRC56XM_011519875.3 linkuse as main transcriptc.-424-2949C>T intron_variant
LRRC56XM_011519877.3 linkuse as main transcriptc.-161-3931C>T intron_variant
LRRC56XM_017017167.2 linkuse as main transcriptc.-499-2874C>T intron_variant

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
HRASENST00000468682.2 linkuse as main transcriptc.-54+1204G>A intron_variant 3
HRASENST00000462734.2 linkuse as main transcriptc.-54+687G>A intron_variant, NMD_transcript_variant 2

Frequencies

GnomAD3 genomes
AF:
0.241
AC:
36626
AN:
151744
Hom.:
4822
Cov.:
33
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:
7
AN:
24
Hom.:
0
AF XY:
0.350
AC XY:
7
AN XY:
20
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.:
33
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 submitterclinical testingGeneDxJun 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

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

Other links and lift over

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