Genetic Variant HGS:c.199-9C>T (chr17-81686994-C-T) – ACMG Classification: Benign (-10 pts)

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_004712.5(HGS):c.199-9C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00873 in 1,610,716 control chromosomes in the GnomAD database, including 90 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0051 ( 5 hom., cov: 33)

Exomes 𝑓: 0.0091 ( 85 hom. )

Consequence

HGS
NM_004712.5 intron

Scores

Splicing: ADA: 0.00003590

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.144

Publications

2 publications found

Variant links:

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]

HGS links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -10 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.8).

BP6

Variant 17-81686994-C-T is Benign according to our data. Variant chr17-81686994-C-T is described in ClinVar as Benign. ClinVar VariationId is 773332.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High AC in GnomAd4 at 783 AD gene.

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.199-9C>T		intron	N/A	NP_004703.1	A0A0S2Z4R4

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
HGS	ENST00000329138.9	TSL:1 MANE Select	c.199-9C>T		intron	N/A	ENSP00000331201.4	O14964-1
HGS	ENST00000678866.1		c.244C>T	p.His82Tyr	missense	Exon 4 of 22	ENSP00000504854.1	A0A7I2V637
HGS	ENST00000677044.1		c.199-9C>T		intron	N/A	ENSP00000504151.1	A0A7I2V5A3

Frequencies

GnomAD3 genomes

AF:

0.00514

AC:

783

AN:

152232

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00188

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00183

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.00248

Gnomad FIN

AF:

0.00132

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00946

Gnomad OTH

AF:

0.00287

GnomAD2 exomes

AF:

0.00565

AC:

1396

AN:

247268

AF XY:

0.00605

show subpopulations

Gnomad AFR exome

AF:

0.00165

Gnomad AMR exome

AF:

0.00222

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00208

Gnomad NFE exome

AF:

0.0100

Gnomad OTH exome

AF:

0.00662

GnomAD4 exome

AF:

0.00911

AC:

13286

AN:

1458366

Hom.:

Cov.:

AF XY:

0.00890

AC XY:

6452

AN XY:

725324

show subpopulations

African (AFR)

AF:

0.00134

AC:

AN:

33458

American (AMR)

AF:

0.00222

AC:

AN:

44548

Ashkenazi Jewish (ASJ)

AF:

0.000115

AC:

AN:

26106

East Asian (EAS)

AF:

0.00

AC:

AN:

39678

South Asian (SAS)

AF:

0.00331

AC:

284

AN:

85740

European-Finnish (FIN)

AF:

0.00209

AC:

110

AN:

52608

Middle Eastern (MID)

AF:

0.00208

AC:

AN:

5758

European-Non Finnish (NFE)

AF:

0.0112

AC:

12401

AN:

1110164

Other (OTH)

AF:

0.00551

AC:

332

AN:

60306

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.469

Heterozygous variant carriers

582

1164

1747

2329

2911

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

462

924

1386

1848

2310

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00514

AC:

783

AN:

152350

Hom.:

Cov.:

AF XY:

0.00466

AC XY:

347

AN XY:

74500

show subpopulations

African (AFR)

AF:

0.00188

AC:

AN:

41582

American (AMR)

AF:

0.00183

AC:

AN:

15310

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.000193

AC:

AN:

5178

South Asian (SAS)

AF:

0.00248

AC:

AN:

4830

European-Finnish (FIN)

AF:

0.00132

AC:

AN:

10624

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00947

AC:

644

AN:

68034

Other (OTH)

AF:

0.00284

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.494

Heterozygous variant carriers

142

190

237

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00750

Hom.:

Bravo

AF:

0.00549

Asia WGS

AF:

0.00115

AC:

AN:

3478

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.80

CADD

Benign

4.5

(source)

DANN

Benign

0.63

PhyloP100

0.14

RBP_binding_hub_radar

0.85

RBP_regulation_power_radar

2.1

Mutation Taster

=100/0

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000036

dbscSNV1_RF

Benign

0.0

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over