rs8070488

Positions:

• chr17-81696901-T-C

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The ENST00000329138.9(HGS):​c.1785T>C​(p.Pro595=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.222 in 1,608,460 control chromosomes in the GnomAD database, including 41,440 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 0.25 (5303 hom., cov: 33)
  • Exomes 𝑓: 0.22 (36137 hom.)
• Consequence: HGS ENST00000329138.9 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -6.42

Genes affected

HGS (HGNC:4897): (hepatocyte growth factor-regulated tyrosine kinase substrate) The protein encoded by this gene regulates endosomal sorting and plays a critical role in the recycling and degradation of membrane receptors. The encoded protein sorts monoubiquitinated membrane proteins into the multivesicular body, targeting these proteins for lysosome-dependent degradation. [provided by RefSeq, Dec 2010]

ACMG classification

Verdict is Benign. Variant got -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.96).
• BP7: Synonymous conserved (PhyloP=-6.41 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.363 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HGS	NM_004712.5	c.1785T>C	p.Pro595=	synonymous_variant	18/22	ENST00000329138.9	NP_004703.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HGS	ENST00000329138.9	c.1785T>C	p.Pro595=	synonymous_variant	18/22	1	NM_004712.5	ENSP00000331201	P1

Frequencies

GnomAD3 genomes AF: 0.253 AC: 38508 AN: 151956 Hom.: 5280 Cov.: 33

Gnomad AFR AF: 0.367

Gnomad AMI AF: 0.238

Gnomad AMR AF: 0.193

Gnomad ASJ AF: 0.173

Gnomad EAS AF: 0.219

Gnomad SAS AF: 0.165

Gnomad FIN AF: 0.213

Gnomad MID AF: 0.275

Gnomad NFE AF: 0.217

Gnomad OTH AF: 0.259

GnomAD3 exomes AF: 0.208 AC: 51092 AN: 245384 Hom.: 5745 AF XY: 0.205 AC XY: 27417 AN XY: 133640

Gnomad AFR exome AF: 0.368

Gnomad AMR exome AF: 0.136

Gnomad ASJ exome AF: 0.171

Gnomad EAS exome AF: 0.216

Gnomad SAS exome AF: 0.165

Gnomad FIN exome AF: 0.222

Gnomad NFE exome AF: 0.219

Gnomad OTH exome AF: 0.210

GnomAD4 exome AF: 0.219 AC: 318745 AN: 1456384 Hom.: 36137 Cov.: 34 AF XY: 0.216 AC XY: 156831 AN XY: 724578

Gnomad4 AFR exome AF: 0.381

Gnomad4 AMR exome AF: 0.142

Gnomad4 ASJ exome AF: 0.177

Gnomad4 EAS exome AF: 0.265

Gnomad4 SAS exome AF: 0.162

Gnomad4 FIN exome AF: 0.219

Gnomad4 NFE exome AF: 0.220

Gnomad4 OTH exome AF: 0.227

GnomAD4 genome AF: 0.254 AC: 38572 AN: 152076 Hom.: 5303 Cov.: 33 AF XY: 0.250 AC XY: 18559 AN XY: 74324

Gnomad4 AFR AF: 0.368

Gnomad4 AMR AF: 0.193

Gnomad4 ASJ AF: 0.173

Gnomad4 EAS AF: 0.219

Gnomad4 SAS AF: 0.165

Gnomad4 FIN AF: 0.213

Gnomad4 NFE AF: 0.217

Gnomad4 OTH AF: 0.257

Alfa AF: 0.224 Hom.: 3990

Bravo AF: 0.260

Asia WGS AF: 0.203 AC: 705 AN: 3478

EpiCase AF: 0.219

EpiControl AF: 0.224

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	0.017
DANN	Benign	0.39
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7

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

Other links and lift over

dbSNP: rs8070488; hg19: chr17-79663931; COSMIC: COSV61267894; COSMIC: COSV61267894;