Genetic Variant NM_002113.3:c.942A>T (chr1-196831948-A-T) – ACMG Classification: Benign (-21 pts)

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_002113.3(CFHR1):c.942A>T(p.Arg314Arg) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.422 in 1,521,694 control chromosomes in the GnomAD database, including 200,105 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.42 ( 17895 hom., cov: 24)

Exomes 𝑓: 0.42 ( 182210 hom. )

Consequence

CFHR1
NM_002113.3 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: 1.46

Publications

16 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
age related macular degeneration 1
Inheritance: Unknown Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae)
hemolytic uremic syndrome, atypical, susceptibility to, 1
Inheritance: Unknown, AD Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics

CFHR1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.96).

BP6

Variant 1-196831948-A-T is Benign according to our data. Variant chr1-196831948-A-T is described in ClinVar as Benign. ClinVar VariationId is 1233842.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=1.46 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.519 is higher than 0.05.

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
CFHR1	NM_002113.3	MANE Select	c.942A>T	p.Arg314Arg	synonymous	Exon 6 of 6	NP_002104.2
CFHR1	NM_001379306.1		c.891A>T	p.Arg297Arg	synonymous	Exon 6 of 6	NP_001366235.1
CFHR1	NM_001379307.1		c.780A>T	p.Arg260Arg	synonymous	Exon 6 of 6	NP_001366236.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
CFHR1	ENST00000320493.10	TSL:1 MANE Select	c.942A>T	p.Arg314Arg	synonymous	Exon 6 of 6	ENSP00000314299.5
CFHR1	ENST00000699454.1		c.780A>T	p.Arg260Arg	synonymous	Exon 6 of 6	ENSP00000514391.1
CFHR1	ENST00000367424.4	TSL:5	c.765A>T	p.Arg255Arg	synonymous	Exon 5 of 5	ENSP00000356394.3

Frequencies

GnomAD3 genomes

AF:

0.422

AC:

56317

AN:

133544

Hom.:

17874

Cov.:

show subpopulations

Gnomad AFR

AF:

0.374

Gnomad AMI

AF:

0.177

Gnomad AMR

AF:

0.529

Gnomad ASJ

AF:

0.516

Gnomad EAS

AF:

0.521

Gnomad SAS

AF:

0.438

Gnomad FIN

AF:

0.380

Gnomad MID

AF:

0.429

Gnomad NFE

AF:

0.417

Gnomad OTH

AF:

0.468

GnomAD2 exomes

AF:

0.438

AC:

103564

AN:

236238

AF XY:

0.436

show subpopulations

Gnomad AFR exome

AF:

0.380

Gnomad AMR exome

AF:

0.509

Gnomad ASJ exome

AF:

0.526

Gnomad EAS exome

AF:

0.524

Gnomad FIN exome

AF:

0.388

Gnomad NFE exome

AF:

0.415

Gnomad OTH exome

AF:

0.436

GnomAD4 exome

AF:

0.422

AC:

586307

AN:

1388030

Hom.:

182210

Cov.:

AF XY:

0.423

AC XY:

291264

AN XY:

689144

show subpopulations

African (AFR)

AF:

0.369

AC:

9710

AN:

26322

American (AMR)

AF:

0.516

AC:

22613

AN:

43852

Ashkenazi Jewish (ASJ)

AF:

0.511

AC:

12362

AN:

24182

East Asian (EAS)

AF:

0.514

AC:

20310

AN:

39482

South Asian (SAS)

AF:

0.420

AC:

32040

AN:

76248

European-Finnish (FIN)

AF:

0.390

AC:

20350

AN:

52142

Middle Eastern (MID)

AF:

0.404

AC:

2056

AN:

5090

European-Non Finnish (NFE)

AF:

0.416

AC:

442356

AN:

1063686

Other (OTH)

AF:

0.430

AC:

24510

AN:

57026

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.442

Heterozygous variant carriers

12848

25696

38545

51393

64241

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

12008

24016

36024

48032

60040

<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:

0.422

AC:

56364

AN:

133664

Hom.:

17895

Cov.:

AF XY:

0.424

AC XY:

27500

AN XY:

64928

show subpopulations

African (AFR)

AF:

0.373

AC:

11577

AN:

31020

American (AMR)

AF:

0.529

AC:

7377

AN:

13936

Ashkenazi Jewish (ASJ)

AF:

0.516

AC:

1620

AN:

3138

East Asian (EAS)

AF:

0.522

AC:

2645

AN:

5064

South Asian (SAS)

AF:

0.439

AC:

1712

AN:

3902

European-Finnish (FIN)

AF:

0.380

AC:

3732

AN:

9820

Middle Eastern (MID)

AF:

0.418

AC:

107

AN:

256

European-Non Finnish (NFE)

AF:

0.417

AC:

26588

AN:

63836

Other (OTH)

AF:

0.470

AC:

850

AN:

1810

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1061

2122

3182

4243

5304

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

456

912

1368

1824

2280

<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:

0.420

Hom.:

1976

Asia WGS

AF:

0.493

AC:

1595

AN:

3236

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:2

Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

Genome Diagnostics Laboratory, University Medical Center Utrecht

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

not provided

Benign:2

Jul 05, 2018

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.96

CADD

Benign

2.1

(source)

DANN

Benign

0.51

PhyloP100

1.5

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

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over