rs12452184

Positions:

• chr17-81697396-C-T

Variant summary

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

The NM_004712.5(HGS):​c.1882+398C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.498 in 145,276 control chromosomes in the GnomAD database, including 18,612 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 0.51 (18319 hom., cov: 22)
  • Exomes 𝑓: 0.20 (293 hom.)
• Consequence: HGS NM_004712.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.889

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]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.665 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HGS	NM_004712.5	c.1882+398C>T		intron_variant		ENST00000329138.9	NP_004703.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HGS	ENST00000329138.9	c.1882+398C>T		intron_variant		1	NM_004712.5	ENSP00000331201	P1
	ENST00000620344.1	n.319G>A		non_coding_transcript_exon_variant	1/1

Frequencies

GnomAD3 genomes AF: 0.513 AC: 70827 AN: 138072 Hom.: 18286 Cov.: 22

Gnomad AFR AF: 0.671

Gnomad AMI AF: 0.371

Gnomad AMR AF: 0.549

Gnomad ASJ AF: 0.505

Gnomad EAS AF: 0.407

Gnomad SAS AF: 0.409

Gnomad FIN AF: 0.466

Gnomad MID AF: 0.604

Gnomad NFE AF: 0.436

Gnomad OTH AF: 0.508

GnomAD4 exome AF: 0.196 AC: 1385 AN: 7080 Hom.: 293 Cov.: 0 AF XY: 0.193 AC XY: 716 AN XY: 3710

Gnomad4 AFR exome AF: 0.393

Gnomad4 AMR exome AF: 0.328

Gnomad4 ASJ exome AF: 0.219

Gnomad4 EAS exome AF: 0.130

Gnomad4 SAS exome AF: 0.231

Gnomad4 FIN exome AF: 0.104

Gnomad4 NFE exome AF: 0.175

Gnomad4 OTH exome AF: 0.209

GnomAD4 genome AF: 0.513 AC: 70911 AN: 138196 Hom.: 18319 Cov.: 22 AF XY: 0.515 AC XY: 33815 AN XY: 65698

Gnomad4 AFR AF: 0.672

Gnomad4 AMR AF: 0.549

Gnomad4 ASJ AF: 0.505

Gnomad4 EAS AF: 0.406

Gnomad4 SAS AF: 0.409

Gnomad4 FIN AF: 0.466

Gnomad4 NFE AF: 0.436

Gnomad4 OTH AF: 0.506

Alfa AF: 0.442 Hom.: 23240

Bravo AF: 0.510

Asia WGS AF: 0.377 AC: 1310 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.92
DANN	Benign	0.69

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: rs12452184; hg19: chr17-79664426;