dbSNP rs80205675: HRG:c.184-11G>T (chr3-186668924-G-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_000412.5(HRG):c.184-11G>T variant causes a 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 intron

Scores

Splicing: ADA: 0.0001642

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.171

Publications

0 publications found

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:

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=-0.69).

BP6

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

BS2

High AC in GnomAd4 at 770 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000412.5. 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
	HRG	NM_000412.5	MANE Select	c.184-11G>T		intron	N/A	NP_000403.1	P04196

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
HRG	ENST00000232003.5	TSL:1 MANE Select	c.184-11G>T	intron	N/A	ENSP00000232003.4	P04196
HRG	ENST00000887868.1		c.184-11G>T	intron	N/A	ENSP00000557927.1
HRG	ENST00000887859.1		c.184-11G>T	intron	N/A	ENSP00000557918.1

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

GnomAD2 exomes

AF:

0.00511

AC:

1284

AN:

251068

AF XY:

0.00494

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 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

African (AFR)

AF:

0.000879

AC:

AN:

30716

American (AMR)

AF:

0.00458

AC:

204

AN:

44566

Ashkenazi Jewish (ASJ)

AF:

0.000277

AC:

AN:

25242

East Asian (EAS)

AF:

0.00

AC:

AN:

39036

South Asian (SAS)

AF:

0.000767

AC:

AN:

83424

European-Finnish (FIN)

AF:

0.00378

AC:

201

AN:

53190

Middle Eastern (MID)

AF:

0.00218

AC:

AN:

5502

European-Non Finnish (NFE)

AF:

0.00928

AC:

9124

AN:

982810

Other (OTH)

AF:

0.00615

AC:

342

AN:

55636

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

463

925

1388

1850

2313

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

318

636

954

1272

1590

<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:

0.00506

AC:

770

AN:

152116

Hom.:

Cov.:

AF XY:

0.00452

AC XY:

336

AN XY:

74364

show subpopulations

African (AFR)

AF:

0.00128

AC:

AN:

41512

American (AMR)

AF:

0.00406

AC:

AN:

15280

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3466

East Asian (EAS)

AF:

0.00

AC:

AN:

5192

South Asian (SAS)

AF:

0.000831

AC:

AN:

4814

European-Finnish (FIN)

AF:

0.00379

AC:

AN:

10558

Middle Eastern (MID)

AF:

0.00340

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00880

AC:

598

AN:

67982

Other (OTH)

AF:

0.00570

AC:

AN:

2106

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

110

147

184

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

100

<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:

0.00742

Hom.:

Bravo

AF:

0.00497

Asia WGS

AF:

0.000577

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

-0.69

CADD

Benign

9.7

(source)

DANN

Benign

0.83

PhyloP100

-0.17

Mutation Taster

=100/0

polymorphism

(source)

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

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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