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rs1061170

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_000186.4(CFH):c.1204C>A(p.His402Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/18 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. H402Y) has been classified as Likely benign.

Frequency

Genomes: not found (cov: 31)

Consequence

CFH
NM_000186.4 missense

Scores

17

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -8.33
Variant links:
Genes affected
CFH (HGNC:4883): (complement factor H) This gene is a member of the Regulator of Complement Activation (RCA) gene cluster and encodes a protein with twenty short consensus repeat (SCR) domains. This protein is secreted into the bloodstream and has an essential role in the regulation of complement activation, restricting this innate defense mechanism to microbial infections. Mutations in this gene have been associated with hemolytic-uremic syndrome (HUS) and chronic hypocomplementemic nephropathy. Alternate transcriptional splice variants, encoding different isoforms, have been characterized. [provided by RefSeq, Oct 2011]

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.12425029).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
CFHNM_000186.4 linkuse as main transcriptc.1204C>A p.His402Asn missense_variant 9/22 ENST00000367429.9
CFHNM_001014975.3 linkuse as main transcriptc.1204C>A p.His402Asn missense_variant 9/10

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
CFHENST00000367429.9 linkuse as main transcriptc.1204C>A p.His402Asn missense_variant 9/221 NM_000186.4 P2

Frequencies

GnomAD3 genomes
Cov.:
31
GnomAD4 exome
Cov.:
50
GnomAD4 genome
Cov.:
31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.069
BayesDel_addAF
Benign
-0.33
T
BayesDel_noAF
Benign
-0.71
Cadd
Benign
0.0010
Dann
Benign
0.34
Eigen
Benign
-2.7
Eigen_PC
Benign
-2.8
FATHMM_MKL
Benign
0.0031
N
LIST_S2
Benign
0.12
T;T;T
M_CAP
Benign
0.050
D
MetaRNN
Benign
0.12
T;T;T
MetaSVM
Benign
-1.1
T
MutationTaster
Benign
1.0
N;N;N
PrimateAI
Benign
0.25
T
PROVEAN
Benign
-0.10
N;.;N
REVEL
Benign
0.067
Sift
Benign
0.53
T;.;T
Sift4G
Benign
0.32
T;T;T
Polyphen
0.0
.;.;B
Vest4
0.12
MutPred
0.57
Loss of catalytic residue at H402 (P = 0.0361);Loss of catalytic residue at H402 (P = 0.0361);.;
MVP
0.43
MPC
0.15
ClinPred
0.018
T
GERP RS
-9.1
gMVP
0.57

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.030
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.

Other links and lift over

dbSNP: rs1061170; hg19: chr1-196659237; API