Variant chr11-532596-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_176795.5(HRAS):c.*179C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00264 in 1,597,530 control chromosomes in the GnomAD database, including 14 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0021 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0027 ( 14 hom. )

Consequence

HRAS
NM_176795.5 3_prime_UTR

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.552

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 -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.81).

BP6

Variant 11-532596-G-A is Benign according to our data. Variant chr11-532596-G-A is described in ClinVar as [Benign]. Clinvar id is 1269148.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.00214 (326/152346) while in subpopulation SAS AF= 0.00642 (31/4832). AF 95% confidence interval is 0.00464. There are 0 homozygotes in gnomad4. There are 163 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High AC in GnomAd4 at 326 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
HRAS	NM_176795.5 linkuse as main transcript	c.*179C>T		3_prime_UTR_variant	6/6	ENST00000417302.7
HRAS	NM_005343.4 linkuse as main transcript	c.*5+35C>T		intron_variant		ENST00000311189.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HRAS	ENST00000417302.7 linkuse as main transcript	c.*179C>T		3_prime_UTR_variant	6/6	5	NM_176795.5		P01112-2
HRAS	ENST00000311189.8 linkuse as main transcript	c.*5+35C>T		intron_variant		1	NM_005343.4	P1	P01112-1

Frequencies

GnomAD3 genomes

AF:

0.00213

AC:

325

AN:

152228

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000410

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00438

Gnomad ASJ

AF:

0.00518

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00620

Gnomad FIN

AF:

0.00169

Gnomad MID

AF:

0.0190

Gnomad NFE

AF:

0.00237

Gnomad OTH

AF:

0.00382

GnomAD3 exomes

AF:

0.00266

AC:

597

AN:

224058

Hom.:

AF XY:

0.00284

AC XY:

351

AN XY:

123450

show subpopulations

Gnomad AFR exome

AF:

0.000357

Gnomad AMR exome

AF:

0.00188

Gnomad ASJ exome

AF:

0.00387

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00538

Gnomad FIN exome

AF:

0.00142

Gnomad NFE exome

AF:

0.00281

Gnomad OTH exome

AF:

0.00514

GnomAD4 exome

AF:

0.00269

AC:

3893

AN:

1445184

Hom.:

Cov.:

AF XY:

0.00275

AC XY:

1979

AN XY:

718892

show subpopulations

Gnomad4 AFR exome

AF:

0.000750

Gnomad4 AMR exome

AF:

0.00188

Gnomad4 ASJ exome

AF:

0.00405

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00581

Gnomad4 FIN exome

AF:

0.00126

Gnomad4 NFE exome

AF:

0.00254

Gnomad4 OTH exome

AF:

0.00342

GnomAD4 genome

AF:

0.00214

AC:

326

AN:

152346

Hom.:

Cov.:

AF XY:

0.00219

AC XY:

163

AN XY:

74506

show subpopulations

Gnomad4 AFR

AF:

0.000409

Gnomad4 AMR

AF:

0.00438

Gnomad4 ASJ

AF:

0.00518

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00642

Gnomad4 FIN

AF:

0.00169

Gnomad4 NFE

AF:

0.00237

Gnomad4 OTH

AF:

0.00378

Alfa

AF:

0.00301

Hom.:

Bravo

AF:

0.00215

Asia WGS

AF:

0.00202

AC:

AN:

3478

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

Dec 13, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.81

CADD

Benign

6.7

DANN

Benign

0.89

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

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