Variant 17-81686994-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_004712.5(HGS):c.199-9C>T variant causes a splice polypyrimidine tract, 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 splice_polypyrimidine_tract, intron

Scores

Splicing: ADA: 0.00003590

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.144

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 made for transcript

Verdict is Benign. Variant got -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 id is 773332.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High AC in GnomAd4 at 783 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
HGS	NM_004712.5 linkuse as main transcript	c.199-9C>T		splice_polypyrimidine_tract_variant, intron_variant		ENST00000329138.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HGS	ENST00000329138.9 linkuse as main transcript	c.199-9C>T		splice_polypyrimidine_tract_variant, intron_variant		1	NM_004712.5	P1	O14964-1

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

GnomAD3 exomes

AF:

0.00565

AC:

1396

AN:

247268

Hom.:

AF XY:

0.00605

AC XY:

811

AN XY:

134056

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 SAS exome

AF:

0.00303

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

Gnomad4 AFR exome

AF:

0.00134

Gnomad4 AMR exome

AF:

0.00222

Gnomad4 ASJ exome

AF:

0.000115

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00331

Gnomad4 FIN exome

AF:

0.00209

Gnomad4 NFE exome

AF:

0.0112

Gnomad4 OTH exome

AF:

0.00551

GnomAD4 genome

AF:

0.00514

AC:

783

AN:

152350

Hom.:

Cov.:

AF XY:

0.00466

AC XY:

347

AN XY:

74500

show subpopulations

Gnomad4 AFR

AF:

0.00188

Gnomad4 AMR

AF:

0.00183

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.00248

Gnomad4 FIN

AF:

0.00132

Gnomad4 NFE

AF:

0.00947

Gnomad4 OTH

AF:

0.00284

Alfa

AF:

0.00750

Hom.:

Bravo

AF:

0.00549

Asia WGS

AF:

0.00115

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jul 06, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.80

CADD

Benign

4.5

DANN

Benign

0.63

RBP_binding_hub_radar

0.85

RBP_regulation_power_radar

2.1

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over