Genetic Variant CFHR3:p.Tyr118Tyr (chr1-196779897-C-T) – ACMG Classification: Benign (-17 pts)

Variant summary

Our verdict is Benign. The variant received -17 ACMG points: 0P and 17B. BP4_StrongBP6_Very_StrongBP7BS2

The NM_021023.6(CFHR3):c.354C>T(p.Tyr118Tyr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000261 in 1,533,054 control chromosomes in the GnomAD database, including 76 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.00026 ( 6 hom., cov: 25)

Exomes 𝑓: 0.00026 ( 70 hom. )

Consequence

CFHR3
NM_021023.6 synonymous

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -1.67

Publications

4 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 -17 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.9).

BP6

Variant 1-196779897-C-T is Benign according to our data. Variant chr1-196779897-C-T is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 761758.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-1.66 with no splicing effect.

BS2

High Homozygotes in GnomAd4 at 6 Unknown gene

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.354C>T	p.Tyr118Tyr	synonymous	Exon 3 of 6	NP_066303.2	Q02985-1
	CFHR3	NM_001166624.2		c.354C>T	p.Tyr118Tyr	synonymous	Exon 3 of 5	NP_001160096.1	Q02985-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
CFHR3	ENST00000367425.9	TSL:1 MANE Select	c.354C>T	p.Tyr118Tyr	synonymous	Exon 3 of 6	ENSP00000356395.5	Q02985-1
ENSG00000289697	ENST00000696032.1		c.3876C>T	p.Tyr1292Tyr	synonymous	Exon 24 of 27	ENSP00000512341.1	A0A8Q3SIA1
CFHR3	ENST00000471440.6	TSL:1	c.354C>T	p.Tyr118Tyr	synonymous	Exon 3 of 5	ENSP00000436258.1	Q6NSD3

Frequencies

GnomAD3 genomes

AF:

0.000256

AC:

AN:

136628

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000920

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000706

Gnomad ASJ

AF:

0.00878

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000465

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.000566

AC:

135

AN:

238676

AF XY:

0.000552

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000411

Gnomad ASJ exome

AF:

0.0113

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000826

Gnomad OTH exome

AF:

0.00103

GnomAD4 exome

AF:

0.000261

AC:

365

AN:

1396426

Hom.:

Cov.:

AF XY:

0.000265

AC XY:

184

AN XY:

693222

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

27838

American (AMR)

AF:

0.000591

AC:

AN:

43996

Ashkenazi Jewish (ASJ)

AF:

0.0104

AC:

253

AN:

24384

East Asian (EAS)

AF:

0.00

AC:

AN:

39572

South Asian (SAS)

AF:

0.00

AC:

AN:

76730

European-Finnish (FIN)

AF:

0.00

AC:

AN:

52478

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5112

European-Non Finnish (NFE)

AF:

0.0000458

AC:

AN:

1068888

Other (OTH)

AF:

0.000644

AC:

AN:

57428

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.467

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:

0.000256

AC:

AN:

136628

Hom.:

Cov.:

AF XY:

0.000226

AC XY:

AN XY:

66386

show subpopulations

African (AFR)

AF:

0.0000920

AC:

AN:

32608

American (AMR)

AF:

0.0000706

AC:

AN:

14170

Ashkenazi Jewish (ASJ)

AF:

0.00878

AC:

AN:

3190

East Asian (EAS)

AF:

0.00

AC:

AN:

5102

South Asian (SAS)

AF:

0.00

AC:

AN:

3888

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10118

Middle Eastern (MID)

AF:

0.00

AC:

AN:

272

European-Non Finnish (NFE)

AF:

0.0000465

AC:

AN:

64542

Other (OTH)

AF:

0.00

AC:

AN:

1848

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.482

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:

0.000272

Hom.:

ClinVar

ClinVar submissions

Significance:Benign/Likely benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (3)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.90

CADD

Benign

4.0

(source)

DANN

Benign

0.20

PhyloP100

-1.7

Mutation Taster

=100/0

polymorphism

(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