rs762653

chrX-153953469-G-AchrX-153953469-G-C

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_005334.3(HCFC1):c.4497+138C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.21 in 584,547 control chromosomes in the GnomAD database, including 14,707 homozygotes. There are 39,881 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., 6318 hem., cov: 24)
  • Exomes 𝑓: 0.22 (12526 hom. 33563 hem.)
• Consequence: HCFC1 NM_005334.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.0880

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

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BP6: Variant X-153953469-G-A is Benign according to our data. Variant chrX-153953469-G-A is described in ClinVar as [Benign]. Clinvar id is 1240591.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.721 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
HCFC1	NM_005334.3	c.4497+138C>T		intron_variant		ENST00000310441.12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HCFC1	ENST00000310441.12	c.4497+138C>T		intron_variant		1	NM_005334.3	P2
HCFC1	ENST00000369984.4	c.4497+138C>T		intron_variant		5		A2
HCFC1	ENST00000444191.5	c.220+138C>T		intron_variant		5

Frequencies

GnomAD3 genomes AF: 0.178 AC: 19879 AN: 111662 Hom.: 2183 Cov.: 24 AF XY: 0.186 AC XY: 6316 AN XY: 33882

Gnomad AFR AF: 0.0700

Gnomad AMI AF: 0.0600

Gnomad AMR AF: 0.406

Gnomad ASJ AF: 0.243

Gnomad EAS AF: 0.746

Gnomad SAS AF: 0.570

Gnomad FIN AF: 0.128

Gnomad MID AF: 0.290

Gnomad NFE AF: 0.142

Gnomad OTH AF: 0.222

GnomAD4 exome AF: 0.218 AC: 102842 AN: 472833 Hom.: 12526 AF XY: 0.255 AC XY: 33563 AN XY: 131835

Gnomad4 AFR exome AF: 0.0680

Gnomad4 AMR exome AF: 0.531

Gnomad4 ASJ exome AF: 0.274

Gnomad4 EAS exome AF: 0.740

Gnomad4 SAS exome AF: 0.561

Gnomad4 FIN exome AF: 0.134

Gnomad4 NFE exome AF: 0.135

Gnomad4 OTH exome AF: 0.240

GnomAD4 genome AF: 0.178 AC: 19871 AN: 111714 Hom.: 2181 Cov.: 24 AF XY: 0.186 AC XY: 6318 AN XY: 33944

Gnomad4 AFR AF: 0.0698

Gnomad4 AMR AF: 0.407

Gnomad4 ASJ AF: 0.243

Gnomad4 EAS AF: 0.745

Gnomad4 SAS AF: 0.567

Gnomad4 FIN AF: 0.128

Gnomad4 NFE AF: 0.142

Gnomad4 OTH AF: 0.224

Alfa AF: 0.0750 Hom.: 382

Bravo AF: 0.200

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 23, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
Cadd	Benign	1.4
Dann	Benign	0.83
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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

Other links and lift over

dbSNP: rs762653; hg19: chrX-153218920; COSMIC: COSV60072021;