Genetic Variant CFHR3:c.253+190A>G (chr1-196779546-A-G) – ACMG Classification: Benign (-14 pts)

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_021023.6(CFHR3):c.253+190A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.281 in 135,410 control chromosomes in the GnomAD database, including 10,821 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.28 ( 10821 hom., cov: 24)

Consequence

CFHR3
NM_021023.6 intron

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.221

Publications

1 publications found

Variant links:

Genes affected

CFHR3 (HGNC:16980): (complement factor H related 3) The protein encoded by this gene is a secreted protein, which belongs to the complement factor H-related protein family. It binds to heparin, and may be involved in complement regulation. Mutations in this gene are associated with decreased risk of age-related macular degeneration, and with an increased risk of atypical hemolytic-uremic syndrome. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Oct 2011]

CFHR3 Gene-Disease associations (from GenCC):

hemolytic uremic syndrome, atypical, susceptibility to, 1
Inheritance: Unknown Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae)

CFHR3 links:

ENSG00000289697 (HGNC:):

ENSG00000289697 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.84).

BP6

Variant 1-196779546-A-G is Benign according to our data. Variant chr1-196779546-A-G is described in ClinVar as Benign. ClinVar VariationId is 1222856.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.488 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_021023.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CFHR3	NM_021023.6	MANE Select	c.253+190A>G		intron	N/A	NP_066303.2	Q02985-1
	CFHR3	NM_001166624.2		c.253+190A>G		intron	N/A	NP_001160096.1	Q02985-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
CFHR3	ENST00000367425.9	TSL:1 MANE Select	c.253+190A>G	intron	N/A	ENSP00000356395.5	Q02985-1
ENSG00000289697	ENST00000696032.1		c.3775+190A>G	intron	N/A	ENSP00000512341.1	A0A8Q3SIA1
CFHR3	ENST00000471440.6	TSL:1	c.253+190A>G	intron	N/A	ENSP00000436258.1	Q6NSD3

Frequencies

GnomAD3 genomes

AF:

0.282

AC:

38088

AN:

135292

Hom.:

10810

Cov.:

show subpopulations

Gnomad AFR

AF:

0.434

Gnomad AMI

AF:

0.286

Gnomad AMR

AF:

0.301

Gnomad ASJ

AF:

0.193

Gnomad EAS

AF:

0.504

Gnomad SAS

AF:

0.214

Gnomad FIN

AF:

0.162

Gnomad MID

AF:

0.260

Gnomad NFE

AF:

0.211

Gnomad OTH

AF:

0.274

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

GnomAD4 genome

AF:

0.281

AC:

38113

AN:

135410

Hom.:

10821

Cov.:

AF XY:

0.280

AC XY:

18430

AN XY:

65896

show subpopulations

African (AFR)

AF:

0.433

AC:

13862

AN:

32012

American (AMR)

AF:

0.301

AC:

4237

AN:

14082

Ashkenazi Jewish (ASJ)

AF:

0.193

AC:

610

AN:

3164

East Asian (EAS)

AF:

0.504

AC:

2557

AN:

5070

South Asian (SAS)

AF:

0.215

AC:

844

AN:

3932

European-Finnish (FIN)

AF:

0.162

AC:

1622

AN:

9988

Middle Eastern (MID)

AF:

0.262

AC:

AN:

244

European-Non Finnish (NFE)

AF:

0.211

AC:

13558

AN:

64172

Other (OTH)

AF:

0.272

AC:

508

AN:

1868

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

850

1700

2549

3399

4249

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

322

644

966

1288

1610

<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:

0.262

Hom.:

1131

Asia WGS

AF:

0.300

AC:

973

AN:

3248

ClinVar

ClinVar submissions

Significance:Benign

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_noAF

Benign

-0.84

CADD

Benign

2.5

(source)

DANN

Benign

0.79

PhyloP100

0.22

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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over