Genetic Variant NM_002113.3:c.130C>T (chr1-196825548-C-T) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BS2

The NM_002113.3(CFHR1):c.130C>T(p.Gln44*) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000101 in 1,521,828 control chromosomes in the GnomAD database, including 50 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Variant results in nonsense mediated mRNA decay.

Frequency

Genomes: 𝑓 0.00049 ( 22 hom., cov: 24)

Exomes 𝑓: 0.000063 ( 28 hom. )

Consequence

CFHR1
NM_002113.3 stop_gained

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.489

Publications

0 publications found

Variant links:

Genes affected

CFHR1 (HGNC:4888): (complement factor H related 1) This gene encodes a secreted protein belonging to the complement factor H protein family. It binds to Pseudomonas aeruginosa elongation factor Tuf together with plasminogen, which is proteolytically activated. It is proposed that Tuf acts as a virulence factor by acquiring host proteins to the pathogen surface, controlling complement, and facilitating tissue invasion. Mutations in this gene are associated with an increased risk of atypical hemolytic-uremic syndrome. [provided by RefSeq, Oct 2009]

CFHR1 Gene-Disease associations (from GenCC):

dense deposit disease
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
hemolytic uremic syndrome, atypical, susceptibility to, 1
Inheritance: AD, Unknown Classification: LIMITED Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae)
age related macular degeneration 1
Inheritance: Unknown Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae)

CFHR1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -4 ACMG points.

BS2

High Homozygotes in GnomAd4 at 22 Unknown,AR,AD gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002113.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
CFHR1	NM_002113.3	MANE Select	c.130C>T	p.Gln44*	stop_gained	Exon 2 of 6	NP_002104.2	Q03591
CFHR1	NM_001379306.1		c.79C>T	p.Gln27*	stop_gained	Exon 2 of 6	NP_001366235.1
CFHR1	NM_001379311.1		c.130C>T	p.Gln44*	stop_gained	Exon 2 of 5	NP_001366240.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
CFHR1	ENST00000320493.10	TSL:1 MANE Select	c.130C>T	p.Gln44*	stop_gained	Exon 2 of 6	ENSP00000314299.5	Q03591
CFHR1	ENST00000887404.1		c.130C>T	p.Gln44*	stop_gained	Exon 2 of 6	ENSP00000557463.1
CFHR1	ENST00000887414.1		c.103C>T	p.Gln35*	stop_gained	Exon 2 of 6	ENSP00000557473.1

Frequencies

GnomAD3 genomes

AF:

0.000488

AC:

AN:

135174

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00199

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000714

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000508

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.000127

AC:

AN:

236278

AF XY:

0.0000863

show subpopulations

Gnomad AFR exome

AF:

0.00184

Gnomad AMR exome

AF:

0.000147

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000627

AC:

AN:

1386534

Hom.:

Cov.:

AF XY:

0.0000639

AC XY:

AN XY:

688572

show subpopulations

African (AFR)

AF:

0.00241

AC:

AN:

26562

American (AMR)

AF:

0.000114

AC:

AN:

43852

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

24188

East Asian (EAS)

AF:

0.00

AC:

AN:

39456

South Asian (SAS)

AF:

0.000158

AC:

AN:

76136

European-Finnish (FIN)

AF:

0.00

AC:

AN:

52132

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5092

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1062132

Other (OTH)

AF:

0.000105

AC:

AN:

56984

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.480

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

<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:

0.000488

AC:

AN:

135294

Hom.:

Cov.:

AF XY:

0.000380

AC XY:

AN XY:

65866

show subpopulations

African (AFR)

AF:

0.00198

AC:

AN:

31778

American (AMR)

AF:

0.0000713

AC:

AN:

14030

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3154

East Asian (EAS)

AF:

0.00

AC:

AN:

5112

South Asian (SAS)

AF:

0.000509

AC:

AN:

3928

European-Finnish (FIN)

AF:

0.00

AC:

AN:

9996

Middle Eastern (MID)

AF:

0.00

AC:

AN:

254

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

64300

Other (OTH)

AF:

0.00

AC:

AN:

1852

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.514

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

<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:

0.000927

Hom.:

ESP6500AA

AF:

0.00299

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.000131

AC:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.034

BayesDel_noAF

Uncertain

-0.030

CADD

Pathogenic

(source)

DANN

Uncertain

1.0

Eigen

Benign

0.15

Eigen_PC

Benign

-0.22

FATHMM_MKL

Benign

0.024

PhyloP100

0.49

Vest4

0.49

GERP RS

1.9

Mutation Taster

=116/84

disease causing (fs/PTC)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.12

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