rs7939028

Positions:

• chr11-536856-G-C

Variant summary

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

The ENST00000468682.2(HRAS):​c.-57C>G variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.245 in 152,248 control chromosomes in the GnomAD database, including 5,015 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 0.24 (5015 hom., cov: 34)
  • Exomes 𝑓: 0.22 (0 hom.)
• Consequence: HRAS ENST00000468682.2 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.975

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=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.349 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LRRC56	XM_011519875.3	c.-424-1742G>C		intron_variant			XP_011518177.1
LRRC56	XM_011519877.3	c.-161-2724G>C		intron_variant			XP_011518179.1
LRRC56	XM_017017167.2	c.-499-1667G>C		intron_variant			XP_016872656.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HRAS	ENST00000468682.2	c.-57C>G		5_prime_UTR_variant	1/3	3		ENSP00000507989.1
HRAS	ENST00000462734.2	n.-574C>G		non_coding_transcript_exon_variant	1/7	2		ENSP00000507303.1
HRAS	ENST00000462734.2	n.-574C>G		5_prime_UTR_variant	1/7	2		ENSP00000507303.1

Frequencies

GnomAD3 genomes AF: 0.245 AC: 37213 AN: 152114 Hom.: 5004 Cov.: 34

Gnomad AFR AF: 0.354

Gnomad AMI AF: 0.268

Gnomad AMR AF: 0.186

Gnomad ASJ AF: 0.167

Gnomad EAS AF: 0.185

Gnomad SAS AF: 0.215

Gnomad FIN AF: 0.178

Gnomad MID AF: 0.245

Gnomad NFE AF: 0.212

Gnomad OTH AF: 0.231

GnomAD4 exome AF: 0.222 AC: 4 AN: 18 Hom.: 0 Cov.: 0 AF XY: 0.200 AC XY: 2 AN XY: 10

Gnomad4 SAS exome AF: 0.500

Gnomad4 NFE exome AF: 0.188

GnomAD4 genome AF: 0.245 AC: 37250 AN: 152230 Hom.: 5015 Cov.: 34 AF XY: 0.243 AC XY: 18081 AN XY: 74440

Gnomad4 AFR AF: 0.354

Gnomad4 AMR AF: 0.185

Gnomad4 ASJ AF: 0.167

Gnomad4 EAS AF: 0.185

Gnomad4 SAS AF: 0.216

Gnomad4 FIN AF: 0.178

Gnomad4 NFE AF: 0.212

Gnomad4 OTH AF: 0.235

Alfa AF: 0.230 Hom.: 527

Bravo AF: 0.247

Asia WGS AF: 0.215 AC: 746 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	2.5
DANN	Benign	0.47

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs7939028; hg19: chr11-536856;