NM_004712.5:c.1882+398C>T

Variant names:

• chr17-81697396-C-T
• rs12452184
• NM_004712.5:c.1882+398C>T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 16 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 -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.

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HGS	NM_004712.5	MANE Select	c.1882+398C>T		intron	N/A	NP_004703.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HGS	ENST00000329138.9	TSL:1 MANE Select	c.1882+398C>T		intron	N/A	ENSP00000331201.4
	HGS	ENST00000571647.1	TSL:6	n.1441C>T		non_coding_transcript_exon	Exon 1 of 1
	ENSG00000275902	ENST00000620344.1	TSL:6	n.319G>A		non_coding_transcript_exon	Exon 1 of 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

African (AFR) AF: 0.393 AC: 70 AN: 178

American (AMR) AF: 0.328 AC: 217 AN: 662

Ashkenazi Jewish (ASJ) AF: 0.219 AC: 42 AN: 192

East Asian (EAS) AF: 0.130 AC: 48 AN: 368

South Asian (SAS) AF: 0.231 AC: 85 AN: 368

European-Finnish (FIN) AF: 0.104 AC: 22 AN: 212

Middle Eastern (MID) AF: 0.0769 AC: 2 AN: 26

European-Non Finnish (NFE) AF: 0.175 AC: 824 AN: 4716

Other (OTH) AF: 0.209 AC: 75 AN: 358

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

African (AFR) AF: 0.672 AC: 25311 AN: 37682

American (AMR) AF: 0.549 AC: 7052 AN: 12840

Ashkenazi Jewish (ASJ) AF: 0.505 AC: 1718 AN: 3404

East Asian (EAS) AF: 0.406 AC: 1727 AN: 4250

South Asian (SAS) AF: 0.409 AC: 1710 AN: 4184

European-Finnish (FIN) AF: 0.466 AC: 3347 AN: 7176

Middle Eastern (MID) AF: 0.592 AC: 154 AN: 260

European-Non Finnish (NFE) AF: 0.436 AC: 28592 AN: 65592

Other (OTH) AF: 0.506 AC: 969 AN: 1916

Alfa AF: 0.456 Hom.: 36038

Bravo AF: 0.510

Asia WGS AF: 0.377 AC: 1310 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.92
DANN	Benign	0.69
PhyloP100		-0.89
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: rs12452184; hg19: chr17-79664426;