rs2071134

Positions:

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_005334.3(HCFC1):c.2283C>G(p.Thr761Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.187 in 1,205,875 control chromosomes in the GnomAD database, including 23,120 homozygotes. There are 78,932 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.18 ( 2181 hom., 6337 hem., cov: 23)

Exomes 𝑓: 0.19 ( 20939 hom. 72595 hem. )

Consequence

HCFC1
NM_005334.3 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: 1.51

Variant links:

Genes affected

HCFC1 (HGNC:4839): (host cell factor C1) This gene is a member of the host cell factor family and encodes a protein with five Kelch repeats, a fibronectin-like motif, and six HCF repeats, each of which contains a highly specific cleavage signal. This nuclear coactivator is proteolytically cleaved at one of the six possible sites, resulting in the creation of an N-terminal chain and the corresponding C-terminal chain. The final form of this protein consists of noncovalently bound N- and C-terminal chains. The protein is involved in control of the cell cycle and transcriptional regulation during herpes simplex virus infection. Alternatively spliced variants which encode different protein isoforms have been described; however, not all variants have been fully characterized. [provided by RefSeq, Jul 2008]

HCFC1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.56).

BP6

Variant X-153957384-G-C is Benign according to our data. Variant chrX-153957384-G-C is described in ClinVar as [Benign]. Clinvar id is 129218.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chrX-153957384-G-C is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=1.51 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.723 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HCFC1	NM_005334.3 linkuse as main transcript	c.2283C>G	p.Thr761Thr	synonymous_variant	13/26	ENST00000310441.12	NP_005325.2	P51610-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HCFC1	ENST00000310441.12 linkuse as main transcript	c.2283C>G	p.Thr761Thr	synonymous_variant	13/26	1	NM_005334.3	ENSP00000309555.7		P51610-1
HCFC1	ENST00000369984.4 linkuse as main transcript	c.2283C>G	p.Thr761Thr	synonymous_variant	13/26	5		ENSP00000359001.4		A6NEM2

Frequencies

GnomAD3 genomes

AF:

0.179

AC:

19912

AN:

111036

Hom.:

2183

Cov.:

AF XY:

0.190

AC XY:

6333

AN XY:

33250

show subpopulations

Gnomad AFR

AF:

0.0700

Gnomad AMI

AF:

0.0611

Gnomad AMR

AF:

0.402

Gnomad ASJ

AF:

0.244

Gnomad EAS

AF:

0.747

Gnomad SAS

AF:

0.587

Gnomad FIN

AF:

0.134

Gnomad MID

AF:

0.297

Gnomad NFE

AF:

0.143

Gnomad OTH

AF:

0.227

GnomAD3 exomes

AF:

0.300

AC:

53992

AN:

179817

Hom.:

8565

AF XY:

0.295

AC XY:

19445

AN XY:

65911

show subpopulations

Gnomad AFR exome

AF:

0.0698

Gnomad AMR exome

AF:

0.579

Gnomad ASJ exome

AF:

0.264

Gnomad EAS exome

AF:

0.752

Gnomad SAS exome

AF:

0.562

Gnomad FIN exome

AF:

0.139

Gnomad NFE exome

AF:

0.143

Gnomad OTH exome

AF:

0.283

GnomAD4 exome

AF:

0.188

AC:

206063

AN:

1094785

Hom.:

20939

Cov.:

AF XY:

0.201

AC XY:

72595

AN XY:

360753

show subpopulations

Gnomad4 AFR exome

AF:

0.0635

Gnomad4 AMR exome

AF:

0.562

Gnomad4 ASJ exome

AF:

0.274

Gnomad4 EAS exome

AF:

0.742

Gnomad4 SAS exome

AF:

0.558

Gnomad4 FIN exome

AF:

0.137

Gnomad4 NFE exome

AF:

0.130

Gnomad4 OTH exome

AF:

0.234

GnomAD4 genome

AF:

0.179

AC:

19906

AN:

111090

Hom.:

2181

Cov.:

AF XY:

0.190

AC XY:

6337

AN XY:

33314

show subpopulations

Gnomad4 AFR

AF:

0.0699

Gnomad4 AMR

AF:

0.403

Gnomad4 ASJ

AF:

0.244

Gnomad4 EAS

AF:

0.747

Gnomad4 SAS

AF:

0.584

Gnomad4 FIN

AF:

0.134

Gnomad4 NFE

AF:

0.143

Gnomad4 OTH

AF:

0.229

Alfa

AF:

0.177

Hom.:

1719

Bravo

AF:

0.200

EpiCase

AF:

0.161

EpiControl

AF:

0.157

ClinVar

Significance: Benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:3

Benign, criteria provided, single submitter	clinical testing	GeneDx	Dec 02, 2015	This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -
Likely benign, no assertion criteria provided	clinical testing	Genetic Services Laboratory, University of Chicago	-	Likely benign based on allele frequency in 1000 Genomes Project or ESP global frequency and its presence in a patient with a rare or unrelated disease phenotype. NOT Sanger confirmed. -
Benign, criteria provided, single submitter	clinical testing	Eurofins Ntd Llc (ga)	Jun 02, 2014	- -

Methylmalonic acidemia with homocystinuria, type cblX

Benign:2

Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Aug 10, 2021	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Feb 01, 2024	- -

not provided

Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.56

CADD

Benign

7.3

DANN

Benign

0.51

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

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