rs3027878

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

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

The NM_005334.3(HCFC1):c.4542G>T(p.Leu1514Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.184 in 1,178,047 control chromosomes in the GnomAD database, including 21,618 homozygotes. There are 75,804 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 ( 2174 hom., 6764 hem., cov: 25)

Exomes 𝑓: 0.18 ( 19444 hom. 69040 hem. )

Consequence

HCFC1
NM_005334.3 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: 0.403

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=-0.6).

BP6

Variant X-153952914-C-A is Benign according to our data. Variant chrX-153952914-C-A is described in ClinVar as [Benign]. Clinvar id is 129222.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chrX-153952914-C-A is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=0.403 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.722 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HCFC1	NM_005334.3 link	c.4542G>T	p.Leu1514Leu	synonymous_variant	Exon 19 of 26	ENST00000310441.12	NP_005325.2	P51610-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
HCFC1	ENST00000310441.12 link	c.4542G>T	p.Leu1514Leu	synonymous_variant	Exon 19 of 26	1	NM_005334.3	ENSP00000309555.7	P51610-1
HCFC1	ENST00000369984.4 link	c.4674G>T	p.Leu1558Leu	synonymous_variant	Exon 19 of 26	5		ENSP00000359001.4	A6NEM2
HCFC1	ENST00000444191.5 link	c.264G>T	p.Leu88Leu	synonymous_variant	Exon 3 of 10	5		ENSP00000399589.1	H7C1C4

Frequencies

GnomAD3 genomes

AF:

0.180

AC:

20308

AN:

112628

Hom.:

2176

Cov.:

AF XY:

0.194

AC XY:

6762

AN XY:

34812

show subpopulations

Gnomad AFR

AF:

0.0703

Gnomad AMI

AF:

0.0599

Gnomad AMR

AF:

0.406

Gnomad ASJ

AF:

0.246

Gnomad EAS

AF:

0.746

Gnomad SAS

AF:

0.588

Gnomad FIN

AF:

0.132

Gnomad MID

AF:

0.293

Gnomad NFE

AF:

0.142

Gnomad OTH

AF:

0.228

GnomAD3 exomes

AF:

0.321

AC:

40409

AN:

125834

Hom.:

6675

AF XY:

0.335

AC XY:

13487

AN XY:

40268

show subpopulations

Gnomad AFR exome

AF:

0.0707

Gnomad AMR exome

AF:

0.574

Gnomad ASJ exome

AF:

0.266

Gnomad EAS exome

AF:

0.749

Gnomad SAS exome

AF:

0.561

Gnomad FIN exome

AF:

0.146

Gnomad NFE exome

AF:

0.145

Gnomad OTH exome

AF:

0.298

GnomAD4 exome

AF:

0.185

AC:

196960

AN:

1065364

Hom.:

19444

Cov.:

AF XY:

0.199

AC XY:

69040

AN XY:

346808

show subpopulations

Gnomad4 AFR exome

AF:

0.0628

Gnomad4 AMR exome

AF:

0.553

Gnomad4 ASJ exome

AF:

0.274

Gnomad4 EAS exome

AF:

0.740

Gnomad4 SAS exome

AF:

0.557

Gnomad4 FIN exome

AF:

0.138

Gnomad4 NFE exome

AF:

0.130

Gnomad4 OTH exome

AF:

0.235

GnomAD4 genome

AF:

0.180

AC:

20300

AN:

112683

Hom.:

2174

Cov.:

AF XY:

0.194

AC XY:

6764

AN XY:

34877

show subpopulations

Gnomad4 AFR

AF:

0.0701

Gnomad4 AMR

AF:

0.407

Gnomad4 ASJ

AF:

0.246

Gnomad4 EAS

AF:

0.746

Gnomad4 SAS

AF:

0.585

Gnomad4 FIN

AF:

0.132

Gnomad4 NFE

AF:

0.142

Gnomad4 OTH

AF:

0.229

Alfa

AF:

0.178

Hom.:

2424

Bravo

AF:

0.200

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:2

Genetic Services Laboratory, University of Chicago

Significance: Likely benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

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. -

Dec 02, 2015

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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. -

Methylmalonic acidemia with homocystinuria, type cblX

Benign:2

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Aug 10, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not provided

Benign:1

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.60

CADD

Benign

1.5

DANN

Benign

0.56

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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