rs8070488

Variant names:

• chr17-81696901-T-C
• rs8070488
• NM_004712.5:c.1785T>C

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_004712.5(HGS):​c.1785T>C​(p.Pro595Pro) 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 NM_004712.5 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -6.42
• Publications: 30 publications found

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]

ENSG00000275902 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004712.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HGS	NM_004712.5	MANE Select	c.1785T>C	p.Pro595Pro	synonymous	Exon 18 of 22	NP_004703.1	A0A0S2Z4R4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HGS	ENST00000329138.9	TSL:1 MANE Select	c.1785T>C	p.Pro595Pro	synonymous	Exon 18 of 22	ENSP00000331201.4	O14964-1
	HGS	ENST00000677044.1		c.1785T>C	p.Pro595Pro	synonymous	Exon 18 of 22	ENSP00000504151.1	A0A7I2V5A3
	HGS	ENST00000678866.1		c.1839T>C	p.Pro613Pro	synonymous	Exon 18 of 22	ENSP00000504854.1	A0A7I2V637

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

GnomAD2 exomes AF: 0.208 AC: 51092 AN: 245384 AF XY: 0.205

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 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

African (AFR) AF: 0.381 AC: 12738 AN: 33436

American (AMR) AF: 0.142 AC: 6318 AN: 44612

Ashkenazi Jewish (ASJ) AF: 0.177 AC: 4621 AN: 26076

East Asian (EAS) AF: 0.265 AC: 10519 AN: 39666

South Asian (SAS) AF: 0.162 AC: 13962 AN: 86160

European-Finnish (FIN) AF: 0.219 AC: 10751 AN: 49102

Middle Eastern (MID) AF: 0.253 AC: 1460 AN: 5760

European-Non Finnish (NFE) AF: 0.220 AC: 244682 AN: 1111268

Other (OTH) AF: 0.227 AC: 13694 AN: 60304

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

African (AFR) AF: 0.368 AC: 15263 AN: 41500

American (AMR) AF: 0.193 AC: 2944 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.173 AC: 598 AN: 3462

East Asian (EAS) AF: 0.219 AC: 1130 AN: 5156

South Asian (SAS) AF: 0.165 AC: 795 AN: 4806

European-Finnish (FIN) AF: 0.213 AC: 2256 AN: 10582

Middle Eastern (MID) AF: 0.272 AC: 80 AN: 294

European-Non Finnish (NFE) AF: 0.217 AC: 14747 AN: 67964

Other (OTH) AF: 0.257 AC: 542 AN: 2112

Alfa AF: 0.228 Hom.: 5291

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	0.017
DANN	Benign	0.39
PhyloP100		-6.4
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

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