Genetic Variant CFHR3:c.*326T>C (chr1-196789156-T-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The ENST00000471440.6(CFHR3):c.*326T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.218 in 971,882 control chromosomes in the GnomAD database, including 46,505 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.28 ( 10933 hom., cov: 24)

Exomes 𝑓: 0.21 ( 35572 hom. )

Consequence

CFHR3
ENST00000471440.6 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.631

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 -12 ACMG points.

BP4

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

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.489 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CFHR3	NM_021023.6 link	c.613+758T>C		intron_variant	Intron 4 of 5	ENST00000367425.9	NP_066303.2
CFHR3	NM_001166624.2 link	c.431-889T>C		intron_variant	Intron 3 of 4		NP_001160096.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CFHR3	ENST00000367425.9 link	c.613+758T>C		intron_variant	Intron 4 of 5	1	NM_021023.6	ENSP00000356395.5
ENSG00000289697	ENST00000696032.1 link	c.4135+758T>C		intron_variant	Intron 25 of 26			ENSP00000512341.1

Frequencies

GnomAD3 genomes

AF:

0.283

AC:

38314

AN:

135574

Hom.:

10920

Cov.:

show subpopulations

Gnomad AFR

AF:

0.436

Gnomad AMI

AF:

0.288

Gnomad AMR

AF:

0.302

Gnomad ASJ

AF:

0.196

Gnomad EAS

AF:

0.506

Gnomad SAS

AF:

0.214

Gnomad FIN

AF:

0.161

Gnomad MID

AF:

0.302

Gnomad NFE

AF:

0.212

Gnomad OTH

AF:

0.268

GnomAD4 exome

AF:

0.207

AC:

173434

AN:

836194

Hom.:

35572

Cov.:

AF XY:

0.206

AC XY:

80904

AN XY:

393078

show subpopulations

African (AFR)

AF:

0.420

AC:

5036

AN:

11986

American (AMR)

AF:

0.315

AC:

1758

AN:

5586

Ashkenazi Jewish (ASJ)

AF:

0.184

AC:

1295

AN:

7020

East Asian (EAS)

AF:

0.489

AC:

4793

AN:

9804

South Asian (SAS)

AF:

0.183

AC:

4184

AN:

22884

European-Finnish (FIN)

AF:

0.142

AC:

883

AN:

6204

Middle Eastern (MID)

AF:

0.212

AC:

341

AN:

1610

European-Non Finnish (NFE)

AF:

0.200

AC:

148513

AN:

741396

Other (OTH)

AF:

0.223

AC:

6631

AN:

29704

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.457

Heterozygous variant carriers

4269

8538

12807

17076

21345

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

5912

11824

17736

23648

29560

<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:

0.283

AC:

38342

AN:

135688

Hom.:

10933

Cov.:

AF XY:

0.281

AC XY:

18566

AN XY:

66034

show subpopulations

African (AFR)

AF:

0.435

AC:

14055

AN:

32294

American (AMR)

AF:

0.302

AC:

4227

AN:

14008

Ashkenazi Jewish (ASJ)

AF:

0.196

AC:

623

AN:

3180

East Asian (EAS)

AF:

0.506

AC:

2554

AN:

5050

South Asian (SAS)

AF:

0.214

AC:

834

AN:

3900

European-Finnish (FIN)

AF:

0.161

AC:

1628

AN:

10084

Middle Eastern (MID)

AF:

0.314

AC:

AN:

242

European-Non Finnish (NFE)

AF:

0.212

AC:

13599

AN:

64194

Other (OTH)

AF:

0.265

AC:

493

AN:

1858

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

846

1692

2539

3385

4231

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:

0.0754

Hom.:

172

Asia WGS

AF:

0.300

AC:

974

AN:

3250

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.96

CADD

Benign

3.2

(source)

DANN

Benign

0.72

PhyloP100

-0.63

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over