rs2071132

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_005334.3(HCFC1):c.5704-42C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.256 in 1,098,077 control chromosomes in the GnomAD database, including 35,729 homozygotes. There are 90,561 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.38 ( 7973 hom., 12973 hem., cov: 24)

Exomes 𝑓: 0.24 ( 27756 hom. 77588 hem. )

Consequence

HCFC1
NM_005334.3 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.194

Publications

6 publications found

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 Gene-Disease associations (from GenCC):

methylmalonic acidemia with homocystinuria, type cblX
Inheritance: XL Classification: DEFINITIVE, STRONG, MODERATE, SUPPORTIVE Submitted by: Orphanet, Labcorp Genetics (formerly Invitae), G2P, Ambry Genetics
X-linked intellectual disability
Inheritance: XL Classification: DEFINITIVE Submitted by: Illumina, ClinGen
non-syndromic X-linked intellectual disability
Inheritance: XL Classification: SUPPORTIVE Submitted by: Orphanet

HCFC1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.89).

BP6

Variant X-153950585-G-A is Benign according to our data. Variant chrX-153950585-G-A is described in ClinVar as Benign. ClinVar VariationId is 1292119.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.736 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005334.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
HCFC1	NM_005334.3	MANE Select	c.5704-42C>T	intron	N/A	NP_005325.2	P51610-1
HCFC1	NM_001440843.1		c.5845-42C>T	intron	N/A	NP_001427772.1
HCFC1	NM_001410705.1		c.5839-42C>T	intron	N/A	NP_001397634.1	A6NEM2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
HCFC1	ENST00000310441.12	TSL:1 MANE Select	c.5704-42C>T	intron	N/A	ENSP00000309555.7	P51610-1
HCFC1	ENST00000925202.1		c.5845-42C>T	intron	N/A	ENSP00000595261.1
HCFC1	ENST00000369984.4	TSL:5	c.5839-42C>T	intron	N/A	ENSP00000359001.4	A6NEM2

Frequencies

GnomAD3 genomes

AF:

0.382

AC:

42596

AN:

111543

Hom.:

7963

Cov.:

show subpopulations

Gnomad AFR

AF:

0.687

Gnomad AMI

AF:

0.0689

Gnomad AMR

AF:

0.498

Gnomad ASJ

AF:

0.255

Gnomad EAS

AF:

0.760

Gnomad SAS

AF:

0.597

Gnomad FIN

AF:

0.175

Gnomad MID

AF:

0.349

Gnomad NFE

AF:

0.180

Gnomad OTH

AF:

0.401

GnomAD2 exomes

AF:

0.377

AC:

47413

AN:

125673

AF XY:

0.348

show subpopulations

Gnomad AFR exome

AF:

0.701

Gnomad AMR exome

AF:

0.620

Gnomad ASJ exome

AF:

0.284

Gnomad EAS exome

AF:

0.761

Gnomad FIN exome

AF:

0.186

Gnomad NFE exome

AF:

0.177

Gnomad OTH exome

AF:

0.326

GnomAD4 exome

AF:

0.242

AC:

238746

AN:

986480

Hom.:

27756

Cov.:

AF XY:

0.266

AC XY:

77588

AN XY:

292138

show subpopulations

African (AFR)

AF:

0.701

AC:

16409

AN:

23404

American (AMR)

AF:

0.604

AC:

14523

AN:

24036

Ashkenazi Jewish (ASJ)

AF:

0.292

AC:

4316

AN:

14769

East Asian (EAS)

AF:

0.750

AC:

22157

AN:

29530

South Asian (SAS)

AF:

0.577

AC:

25477

AN:

44181

European-Finnish (FIN)

AF:

0.179

AC:

6617

AN:

36925

Middle Eastern (MID)

AF:

0.423

AC:

1530

AN:

3614

European-Non Finnish (NFE)

AF:

0.175

AC:

134808

AN:

768258

Other (OTH)

AF:

0.309

AC:

12909

AN:

41763

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

5755

11510

17265

23020

28775

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

5714

11428

17142

22856

28570

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.382

AC:

42656

AN:

111597

Hom.:

7973

Cov.:

AF XY:

0.383

AC XY:

12973

AN XY:

33831

show subpopulations

African (AFR)

AF:

0.687

AC:

21051

AN:

30632

American (AMR)

AF:

0.498

AC:

5293

AN:

10624

Ashkenazi Jewish (ASJ)

AF:

0.255

AC:

675

AN:

2644

East Asian (EAS)

AF:

0.760

AC:

2663

AN:

3505

South Asian (SAS)

AF:

0.594

AC:

1606

AN:

2704

European-Finnish (FIN)

AF:

0.175

AC:

1067

AN:

6086

Middle Eastern (MID)

AF:

0.355

AC:

AN:

211

European-Non Finnish (NFE)

AF:

0.180

AC:

9554

AN:

52987

Other (OTH)

AF:

0.411

AC:

625

AN:

1522

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

748

1496

2243

2991

3739

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

402

804

1206

1608

2010

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.261

Hom.:

3844

Bravo

AF:

0.423

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.89

CADD

Benign

0.28

(source)

DANN

Benign

0.20

PhyloP100

-0.19

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over