Variant chr3-186668924-G-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_000412.5(HRG):c.184-11G>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 0.0073 in 1,472,238 control chromosomes in the GnomAD database, including 53 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0051 ( 4 hom., cov: 32)

Exomes 𝑓: 0.0076 ( 49 hom. )

Consequence

HRG
NM_000412.5 splice_polypyrimidine_tract, intron

Scores

Splicing: ADA: 0.0001642

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.171

Variant links:

Genes affected

HRG (HGNC:5181): (histidine rich glycoprotein) This histidine-rich glycoprotein contains two cystatin-like domains and is located in plasma and platelets. The physiological function has not been determined but it is known that the protein binds heme, dyes and divalent metal ions. The encoded protein also has a peptide that displays antimicrobial activity against C. albicans, E. coli, S. aureus, P. aeruginosa, and E. faecalis. It can inhibit rosette formation and interacts with heparin, thrombospondin and plasminogen. Two of the protein's effects, the inhibition of fibrinolysis and the reduction of inhibition of coagulation, indicate a potential prothrombotic effect. Mutations in this gene lead to thrombophilia due to abnormal histidine-rich glycoprotein levels. [provided by RefSeq, Nov 2014]

HRG links:

HRG-AS1 (HGNC:55915): (HRG and FETUB antisense RNA 1)

HRG-AS1 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.69).

BP6

Variant 3-186668924-G-T is Benign according to our data. Variant chr3-186668924-G-T is described in ClinVar as [Benign]. Clinvar id is 1234952.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High AC in GnomAd4 at 770 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	MANE	Protein
HRG	NM_000412.5 linkuse as main transcript	c.184-11G>T	splice_polypyrimidine_tract_variant, intron_variant	ENST00000232003.5	NP_000403.1
HRG-AS1	XR_924801.3 linkuse as main transcript	n.291-17053C>A	intron_variant, non_coding_transcript_variant
HRG	XM_005247415.5 linkuse as main transcript	c.184-11G>T	splice_polypyrimidine_tract_variant, intron_variant		XP_005247472.1
HRG-AS1	XR_001741059.2 linkuse as main transcript	n.291-17053C>A	intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HRG	ENST00000232003.5 linkuse as main transcript	c.184-11G>T		splice_polypyrimidine_tract_variant, intron_variant		1	NM_000412.5	ENSP00000232003	P1
HRG-AS1	ENST00000630178.2 linkuse as main transcript	n.238+49543C>A		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes

AF:

0.00507

AC:

770

AN:

152002

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00128

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00406

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000830

Gnomad FIN

AF:

0.00379

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.00880

Gnomad OTH

AF:

0.00575

GnomAD3 exomes

AF:

0.00511

AC:

1284

AN:

251068

Hom.:

AF XY:

0.00494

AC XY:

670

AN XY:

135722

show subpopulations

Gnomad AFR exome

AF:

0.000984

Gnomad AMR exome

AF:

0.00451

Gnomad ASJ exome

AF:

0.000199

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000653

Gnomad FIN exome

AF:

0.00325

Gnomad NFE exome

AF:

0.00871

Gnomad OTH exome

AF:

0.00507

GnomAD4 exome

AF:

0.00756

AC:

9981

AN:

1320122

Hom.:

Cov.:

AF XY:

0.00722

AC XY:

4803

AN XY:

664888

show subpopulations

Gnomad4 AFR exome

AF:

0.000879

Gnomad4 AMR exome

AF:

0.00458

Gnomad4 ASJ exome

AF:

0.000277

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000767

Gnomad4 FIN exome

AF:

0.00378

Gnomad4 NFE exome

AF:

0.00928

Gnomad4 OTH exome

AF:

0.00615

GnomAD4 genome

AF:

0.00506

AC:

770

AN:

152116

Hom.:

Cov.:

AF XY:

0.00452

AC XY:

336

AN XY:

74364

show subpopulations

Gnomad4 AFR

AF:

0.00128

Gnomad4 AMR

AF:

0.00406

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000831

Gnomad4 FIN

AF:

0.00379

Gnomad4 NFE

AF:

0.00880

Gnomad4 OTH

AF:

0.00570

Alfa

AF:

0.00755

Hom.:

Bravo

AF:

0.00497

Asia WGS

AF:

0.000577

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

GeneDx

Mar 03, 2015

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.69

CADD

Benign

9.7

DANN

Benign

0.83

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.00016

dbscSNV1_RF

Benign

0.17

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