Variant 4-3442865-C-G 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_001528.4(HGFAC):c.251C>G(p.Pro84Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00519 in 1,572,816 control chromosomes in the GnomAD database, including 32 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0045 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0053 ( 32 hom. )

Consequence

HGFAC
NM_001528.4 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -1.50

Variant links:

Genes affected

HGFAC (HGNC:4894): (HGF activator) This gene encodes a member of the peptidase S1 protein family. The encoded protein is first synthesized as an inactive single-chain precursor before being activated to a heterodimeric form by endoproteolytic processing. It acts as serine protease that converts hepatocyte growth factor to the active form. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jul 2014]

HGFAC 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 (MetaRNN=0.005406052).

BP6

Variant 4-3442865-C-G is Benign according to our data. Variant chr4-3442865-C-G is described in ClinVar as [Likely_benign]. Clinvar id is 2654602.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAdExome4 at 32 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HGFAC	NM_001528.4 linkuse as main transcript	c.251C>G	p.Pro84Arg	missense_variant	2/14	ENST00000382774.8	NP_001519.1	Q04756
HGFAC	NM_001297439.2 linkuse as main transcript	c.251C>G	p.Pro84Arg	missense_variant	2/15		NP_001284368.1	Q04756D6RAR4
HGFAC	XM_047450155.1 linkuse as main transcript	c.-101C>G		5_prime_UTR_variant	2/14		XP_047306111.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HGFAC	ENST00000382774.8 linkuse as main transcript	c.251C>G	p.Pro84Arg	missense_variant	2/14	1	NM_001528.4	ENSP00000372224.4		Q04756
HGFAC	ENST00000511533.1 linkuse as main transcript	c.251C>G	p.Pro84Arg	missense_variant	2/15	1		ENSP00000421801.1		D6RAR4

Frequencies

GnomAD3 genomes

AF:

0.00448

AC:

682

AN:

152138

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00135

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00562

Gnomad ASJ

AF:

0.00662

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00166

Gnomad FIN

AF:

0.00433

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00662

Gnomad OTH

AF:

0.00622

GnomAD3 exomes

AF:

0.00416

AC:

881

AN:

211582

Hom.:

AF XY:

0.00434

AC XY:

501

AN XY:

115496

show subpopulations

Gnomad AFR exome

AF:

0.000930

Gnomad AMR exome

AF:

0.00392

Gnomad ASJ exome

AF:

0.00713

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00197

Gnomad FIN exome

AF:

0.00292

Gnomad NFE exome

AF:

0.00581

Gnomad OTH exome

AF:

0.00702

GnomAD4 exome

AF:

0.00527

AC:

7488

AN:

1420560

Hom.:

Cov.:

AF XY:

0.00517

AC XY:

3648

AN XY:

705046

show subpopulations

Gnomad4 AFR exome

AF:

0.000802

Gnomad4 AMR exome

AF:

0.00396

Gnomad4 ASJ exome

AF:

0.00662

Gnomad4 EAS exome

AF:

0.0000255

Gnomad4 SAS exome

AF:

0.00163

Gnomad4 FIN exome

AF:

0.00402

Gnomad4 NFE exome

AF:

0.00595

Gnomad4 OTH exome

AF:

0.00511

GnomAD4 genome

AF:

0.00448

AC:

682

AN:

152256

Hom.:

Cov.:

AF XY:

0.00424

AC XY:

316

AN XY:

74450

show subpopulations

Gnomad4 AFR

AF:

0.00135

Gnomad4 AMR

AF:

0.00562

Gnomad4 ASJ

AF:

0.00662

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00166

Gnomad4 FIN

AF:

0.00433

Gnomad4 NFE

AF:

0.00662

Gnomad4 OTH

AF:

0.00616

Alfa

AF:

0.00354

Hom.:

Bravo

AF:

0.00407

TwinsUK

AF:

0.00512

AC:

ALSPAC

AF:

0.00545

AC:

ESP6500AA

AF:

0.00136

AC:

ESP6500EA

AF:

0.00616

AC:

ExAC

AF:

0.00386

AC:

468

Asia WGS

AF:

0.000866

AC:

AN:

3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Apr 01, 2023

HGFAC: BP4, BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.065

BayesDel_addAF

Benign

-0.43

BayesDel_noAF

Benign

-0.38

CADD

Benign

0.027

DANN

Benign

0.69

DEOGEN2

Benign

0.036

T;.

Eigen

Benign

-1.4

Eigen_PC

Benign

-1.6

FATHMM_MKL

Benign

0.055

LIST_S2

Benign

0.43

T;T

M_CAP

Uncertain

0.15

MetaRNN

Benign

0.0054

T;T

MetaSVM

Benign

-0.62

MutationAssessor

Benign

0.55

N;.

PrimateAI

Benign

0.34

PROVEAN

Benign

-0.56

N;N

REVEL

Benign

0.28

Sift

Benign

0.061

T;T

Sift4G

Benign

0.31

T;T

Polyphen

0.43

B;B

Vest4

0.24

MVP

0.49

MPC

0.046

ClinPred

0.0022

GERP RS

-2.5

Varity_R

0.035

gMVP

0.29

Splicing

Name

Calibrated prediction

Score

Prediction

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