rs371163886

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2

The NM_005334.3(HCFC1):c.503+14C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000978 in 1,185,008 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 363 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.00068 ( 0 hom., 12 hem., cov: 24)

Exomes 𝑓: 0.0010 ( 0 hom. 351 hem. )

Consequence

HCFC1
NM_005334.3 intron

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 1.50

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 -16 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.81).

BP6

Variant X-153964110-G-C is Benign according to our data. Variant chrX-153964110-G-C is described in ClinVar as [Likely_benign]. Clinvar id is 445538.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High Hemizygotes in GnomAd at 12 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
HCFC1	NM_005334.3 linkuse as main transcript	c.503+14C>G		intron_variant		ENST00000310441.12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HCFC1	ENST00000310441.12 linkuse as main transcript	c.503+14C>G		intron_variant		1	NM_005334.3	P2	P51610-1
HCFC1	ENST00000369984.4 linkuse as main transcript	c.503+14C>G		intron_variant		5		A2

Frequencies

GnomAD3 genomes

AF:

0.000676

AC:

AN:

112448

Hom.:

Cov.:

AF XY:

0.000347

AC XY:

AN XY:

34608

show subpopulations

Gnomad AFR

AF:

0.0000646

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000281

Gnomad ASJ

AF:

0.000754

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000486

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00122

Gnomad OTH

AF:

0.000657

GnomAD3 exomes

AF:

0.000836

AC:

135

AN:

161534

Hom.:

AF XY:

0.000858

AC XY:

AN XY:

50124

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000861

Gnomad ASJ exome

AF:

0.00282

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.000994

Gnomad NFE exome

AF:

0.00106

Gnomad OTH exome

AF:

0.00102

GnomAD4 exome

AF:

0.00101

AC:

1083

AN:

1072508

Hom.:

Cov.:

AF XY:

0.00102

AC XY:

351

AN XY:

343240

show subpopulations

Gnomad4 AFR exome

AF:

0.0000388

Gnomad4 AMR exome

AF:

0.000718

Gnomad4 ASJ exome

AF:

0.00304

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.000774

Gnomad4 NFE exome

AF:

0.00111

Gnomad4 OTH exome

AF:

0.00129

GnomAD4 genome

AF:

0.000676

AC:

AN:

112500

Hom.:

Cov.:

AF XY:

0.000346

AC XY:

AN XY:

34670

show subpopulations

Gnomad4 AFR

AF:

0.0000645

Gnomad4 AMR

AF:

0.000280

Gnomad4 ASJ

AF:

0.000754

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.000486

Gnomad4 NFE

AF:

0.00122

Gnomad4 OTH

AF:

0.000649

Alfa

AF:

0.00113

Hom.:

Bravo

AF:

0.000589

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

Nov 29, 2017

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:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jan 31, 2024

- -

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics

Aug 14, 2017

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.81

Cadd

Benign

2.3

Dann

Benign

0.53

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.2

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