Variant rs748096320 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_021023.6(CFHR3):c.106G>C(p.Glu36Gln) variant causes a missense change. The variant allele was found at a frequency of 0.000000718 in 1,393,010 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. E36K) has been classified as Likely benign.

Frequency

Genomes: not found (cov: 25)

Exomes 𝑓: 7.2e-7 ( 0 hom. )

Consequence

CFHR3
NM_021023.6 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 4.03

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 links:

ENSG00000289697 (HGNC:):

ENSG00000289697 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.28805783).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CFHR3	NM_021023.6 link	c.106G>C	p.Glu36Gln	missense_variant	Exon 2 of 6	ENST00000367425.9	NP_066303.2	Q02985-1
CFHR3	NM_001166624.2 link	c.106G>C	p.Glu36Gln	missense_variant	Exon 2 of 5		NP_001160096.1	Q02985-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CFHR3	ENST00000367425.9 link	c.106G>C	p.Glu36Gln	missense_variant	Exon 2 of 6	1	NM_021023.6	ENSP00000356395.5		Q02985-1
ENSG00000289697	ENST00000696032.1 link	c.3628G>C	p.Glu1210Gln	missense_variant	Exon 23 of 27			ENSP00000512341.1		A0A8Q3SIA1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000420

AC:

AN:

238176

Hom.:

AF XY:

0.00000779

AC XY:

AN XY:

128418

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000368

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

7.18e-7

AC:

AN:

1393010

Hom.:

Cov.:

AF XY:

0.00000145

AC XY:

AN XY:

691760

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000131

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ExAC

AF:

0.00000865

AC:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.18

BayesDel_addAF

Benign

-0.18

BayesDel_noAF

Benign

-0.39

CADD

Benign

DANN

Uncertain

0.98

DEOGEN2

Benign

0.15

T;T;.;T

Eigen

Benign

-0.31

Eigen_PC

Benign

-0.58

FATHMM_MKL

Benign

0.10

LIST_S2

Benign

0.64

T;.;T;T

M_CAP

Benign

0.050

MetaRNN

Benign

0.29

T;T;T;T

MetaSVM

Benign

-0.60

MutationAssessor

Uncertain

2.5

M;.;M;.

PrimateAI

Benign

0.42

PROVEAN

Uncertain

-2.5

N;N;D;.

REVEL

Benign

0.23

Sift

Uncertain

0.011

D;D;D;.

Sift4G

Uncertain

0.013

D;T;D;T

Polyphen

0.96

D;P;.;.

Vest4

0.19

MutPred

0.65

Loss of loop (P = 0.1242);Loss of loop (P = 0.1242);Loss of loop (P = 0.1242);Loss of loop (P = 0.1242);

MVP

0.68

MPC

0.16

ClinPred

0.38

GERP RS

1.3

Varity_R

0.13

gMVP

0.69

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over