rs2266886

Variant names:

• chrX-153965901-T-C
• rs2266886
• NM_005334.3:c.194-1175A>G

Your query was ambiguous. Multiple possible variants found:

• chrX-153965901-T-C
• chrX-153965901-T-G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_005334.3(HCFC1):​c.194-1175A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.382 in 111,262 control chromosomes in the GnomAD database, including 7,994 homozygotes. There are 12,783 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.38 (7994 hom., 12783 hem., cov: 23)
• Consequence: HCFC1 NM_005334.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.72
• Publications: 5 publications found

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 Gene-Disease associations (from GenCC):

• methylmalonic acidemia with homocystinuria, type cblX

  Inheritance: XL Classification: DEFINITIVE, STRONG, MODERATE, SUPPORTIVE Submitted by: G2P, Ambry Genetics, Orphanet, Labcorp Genetics (formerly Invitae)
• X-linked intellectual disability

  Inheritance: XL Classification: DEFINITIVE Submitted by: ClinGen, Illumina
• non-syndromic X-linked intellectual disability

  Inheritance: XL Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.738 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HCFC1	NM_005334.3	c.194-1175A>G		intron_variant	Intron 1 of 25	ENST00000310441.12	NP_005325.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HCFC1	ENST00000310441.12	c.194-1175A>G		intron_variant	Intron 1 of 25	1	NM_005334.3	ENSP00000309555.7
HCFC1	ENST00000369984.4	c.194-1175A>G		intron_variant	Intron 1 of 25	5		ENSP00000359001.4

Frequencies

GnomAD3 genomes AF: 0.382 AC: 42433 AN: 111207 Hom.: 7985 Cov.: 23

Gnomad AFR AF: 0.687

Gnomad AMI AF: 0.0674

Gnomad AMR AF: 0.499

Gnomad ASJ AF: 0.256

Gnomad EAS AF: 0.762

Gnomad SAS AF: 0.607

Gnomad FIN AF: 0.172

Gnomad MID AF: 0.354

Gnomad NFE AF: 0.180

Gnomad OTH AF: 0.406

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.382 AC: 42494 AN: 111262 Hom.: 7994 Cov.: 23 AF XY: 0.381 AC XY: 12783 AN XY: 33530

African (AFR) AF: 0.687 AC: 20951 AN: 30479

American (AMR) AF: 0.499 AC: 5262 AN: 10540

Ashkenazi Jewish (ASJ) AF: 0.256 AC: 675 AN: 2635

East Asian (EAS) AF: 0.762 AC: 2671 AN: 3506

South Asian (SAS) AF: 0.604 AC: 1616 AN: 2675

European-Finnish (FIN) AF: 0.172 AC: 1045 AN: 6067

Middle Eastern (MID) AF: 0.364 AC: 79 AN: 217

European-Non Finnish (NFE) AF: 0.180 AC: 9514 AN: 52933

Other (OTH) AF: 0.416 AC: 635 AN: 1528

Alfa AF: 0.214 Hom.: 9115

Bravo AF: 0.424

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.31
DANN	Benign	0.28
PhyloP100		-1.7
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2266886; hg19: chrX-153231352;