3-186669943-C-T

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_ModerateBP6_ModerateBP7BS1BS2

The NM_000412.5(HRG):c.306C>T(p.Ile102=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0012 in 1,565,278 control chromosomes in the GnomAD database, including 16 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0062 ( 9 hom., cov: 32)

Exomes 𝑓: 0.00066 ( 7 hom. )

Consequence

HRG
NM_000412.5 synonymous

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -1.45

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 made for transcript

Verdict is Benign. Variant got -13 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.37).

BP6

Variant 3-186669943-C-T is Benign according to our data. Variant chr3-186669943-C-T is described in ClinVar as [Benign]. Clinvar id is 786027.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=-1.45 with no splicing effect.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00617 (939/152262) while in subpopulation AFR AF= 0.0211 (876/41532). AF 95% confidence interval is 0.0199. There are 9 homozygotes in gnomad4. There are 439 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High AC in GnomAd at 943 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
HRG	NM_000412.5 linkuse as main transcript	c.306C>T	p.Ile102=	synonymous_variant	3/7	ENST00000232003.5
HRG-AS1	XR_924801.3 linkuse as main transcript	n.291-18072G>A		intron_variant, non_coding_transcript_variant
HRG	XM_005247415.5 linkuse as main transcript	c.306C>T	p.Ile102=	synonymous_variant	3/7
HRG-AS1	XR_001741059.2 linkuse as main transcript	n.291-18072G>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HRG	ENST00000232003.5 linkuse as main transcript	c.306C>T	p.Ile102=	synonymous_variant	3/7	1	NM_000412.5	P1
HRG-AS1	ENST00000630178.2 linkuse as main transcript	n.238+48524G>A		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes

AF:

0.00620

AC:

943

AN:

152144

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0212

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00275

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000415

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000132

Gnomad OTH

AF:

0.00526

GnomAD3 exomes

AF:

0.00169

AC:

424

AN:

250862

Hom.:

AF XY:

0.00120

AC XY:

163

AN XY:

135560

show subpopulations

Gnomad AFR exome

AF:

0.0218

Gnomad AMR exome

AF:

0.00136

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000327

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000132

Gnomad OTH exome

AF:

0.00115

GnomAD4 exome

AF:

0.000661

AC:

934

AN:

1413016

Hom.:

Cov.:

AF XY:

0.000587

AC XY:

414

AN XY:

705836

show subpopulations

Gnomad4 AFR exome

AF:

0.0211

Gnomad4 AMR exome

AF:

0.00154

Gnomad4 ASJ exome

AF:

0.0000387

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000939

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000767

Gnomad4 OTH exome

AF:

0.00152

GnomAD4 genome

AF:

0.00617

AC:

939

AN:

152262

Hom.:

Cov.:

AF XY:

0.00590

AC XY:

439

AN XY:

74466

show subpopulations

Gnomad4 AFR

AF:

0.0211

Gnomad4 AMR

AF:

0.00274

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000208

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000132

Gnomad4 OTH

AF:

0.00521

Alfa

AF:

0.00234

Hom.:

Bravo

AF:

0.00731

Asia WGS

AF:

0.000578

AC:

AN:

3476

EpiCase

AF:

0.0000545

EpiControl

AF:

0.000119

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

Invitae

Apr 17, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.37

Cadd

Benign

0.77

Dann

Benign

0.80

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.050

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