rs3027878

Variant names:

• chrX-153952914-C-A
• rs3027878
• NM_005334.3:c.4542G>T

Your query was ambiguous. Multiple possible variants found:

• chrX-153952914-C-A
• chrX-153952914-C-G

Variant summary

Our verdict is Benign. The variant received -19 ACMG points: 0P and 19B. BP4_Moderate BP6_Very_Strong BP7 BA1

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 (★★). Synonymous variant affecting the same amino acid position (i.e. L1514L) has been classified as Likely 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
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: 0.403

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]

ACMG classification

Our verdict: Benign. The variant received -19 ACMG points.

• BP4: Computational evidence support a benign effect (REVEL=0.054).
• 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	c.4542G>T	p.Leu1514Leu	synonymous_variant	Exon 19 of 26	ENST00000310441.12	NP_005325.2

Ensembl

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

Frequencies

GnomAD3 genomes AF: 0.180 AC: 20308 AN: 112628 Hom.: 2176 Cov.: 25

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

GnomAD2 exomes AF: 0.321 AC: 40409 AN: 125834 AF XY: 0.335

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 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.: 32 AF XY: 0.199 AC XY: 69040 AN XY: 346808

Gnomad4 AFR exome AF: 0.0628 AC: 1603 AN: 25521

Gnomad4 AMR exome AF: 0.553 AC: 16741 AN: 30273

Gnomad4 ASJ exome AF: 0.274 AC: 5182 AN: 18880

Gnomad4 EAS exome AF: 0.740 AC: 20888 AN: 28213

Gnomad4 SAS exome AF: 0.557 AC: 28469 AN: 51081

Gnomad4 FIN exome AF: 0.138 AC: 4930 AN: 35655

Gnomad4 NFE exome AF: 0.130 AC: 107063 AN: 826707

Gnomad4 Remaining exome AF: 0.235 AC: 10553 AN: 44928

GnomAD4 genome AF: 0.180 AC: 20300 AN: 112683 Hom.: 2174 Cov.: 25 AF XY: 0.194 AC XY: 6764 AN XY: 34877

Gnomad4 AFR AF: 0.0701 AC: 0.0701163 AN: 0.0701163

Gnomad4 AMR AF: 0.407 AC: 0.407015 AN: 0.407015

Gnomad4 ASJ AF: 0.246 AC: 0.245766 AN: 0.245766

Gnomad4 EAS AF: 0.746 AC: 0.745614 AN: 0.745614

Gnomad4 SAS AF: 0.585 AC: 0.584906 AN: 0.584906

Gnomad4 FIN AF: 0.132 AC: 0.131773 AN: 0.131773

Gnomad4 NFE AF: 0.142 AC: 0.142177 AN: 0.142177

Gnomad4 OTH AF: 0.229 AC: 0.229476 AN: 0.229476

Alfa AF: 0.173 Hom.: 2501

Bravo AF: 0.200

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:2

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. -

-

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. -

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
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs3027878; hg19: chrX-153218365; COSMIC: COSV60075244;