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GeneBe

rs800292

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_000186(CFH):c.184G>A(p.Val62Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.397 in 151828 control chromosomes in the gnomAD Genomes database, including 15151 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/17 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (β˜…β˜…). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.40 ( 15151 hom., cov: 31)
Exomes 𝑓: 0.32 ( 14648 hom. )

Consequence

CFH
NM_000186 missense

Scores

1
15

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:12O:2

Conservation

PhyloP100: 1.60

Links

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4
?
Computational evidence support a benign effect (MetaRNN=5.604542E-6).
BP6
?
Variant 1:196673103-G>A is Benign according to our data. Variant chr1-196673103-G-A is described in ClinVar as [Benign]. Clinvar id is 16550. Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr1-196673103-G-A is described in Lovd as [Benign].
BA1
?
GnomAd highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.709 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
CFHNM_000186.4 linkuse as main transcriptc.184G>A p.Val62Ile missense_variant 2/22 ENST00000367429.9
CFHNM_001014975.3 linkuse as main transcriptc.184G>A p.Val62Ile missense_variant 2/10
CFHXM_017001108.3 linkuse as main transcriptc.184G>A p.Val62Ile missense_variant 2/10
CFHXR_007059267.1 linkuse as main transcriptn.259G>A non_coding_transcript_exon_variant 2/13

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
CFHENST00000367429.9 linkuse as main transcriptc.184G>A p.Val62Ile missense_variant 2/221 NM_000186.4 P2

Frequencies

GnomAD3 genomes
AF:
0.397
AC:
60251
AN:
151828
Hom.:
15151
Cov.:
31
show subpopulations
Gnomad AFR
AF:
0.716
Gnomad AMI
AF:
0.294
Gnomad AMR
AF:
0.388
Gnomad ASJ
AF:
0.270
Gnomad EAS
AF:
0.423
Gnomad SAS
AF:
0.326
Gnomad FIN
AF:
0.296
Gnomad MID
AF:
0.152
Gnomad NFE
AF:
0.234
Gnomad OTH
AF:
0.357
GnomAD3 exomes
AF:
0.317
AC:
79518
AN:
250544
Hom.:
14648
AF XY:
0.305
AC XY:
41348
AN XY:
135430
show subpopulations
Gnomad AFR exome
AF:
0.725
Gnomad AMR exome
AF:
0.375
Gnomad ASJ exome
AF:
0.269
Gnomad EAS exome
AF:
0.421
Gnomad SAS exome
AF:
0.314
Gnomad FIN exome
AF:
0.302
Gnomad NFE exome
AF:
0.235
Gnomad OTH exome
AF:
0.271
GnomAD4 exome
AF:
0.261
AC:
381288
AN:
1460412
Hom.:
55785
AF XY:
0.261
AC XY:
189294
AN XY:
726594
show subpopulations
Gnomad4 AFR exome
AF:
0.734
Gnomad4 AMR exome
AF:
0.381
Gnomad4 ASJ exome
AF:
0.264
Gnomad4 EAS exome
AF:
0.415
Gnomad4 SAS exome
AF:
0.314
Gnomad4 FIN exome
AF:
0.296
Gnomad4 NFE exome
AF:
0.230
Gnomad4 OTH exome
AF:
0.282
Alfa
AF:
0.253
Hom.:
14695
Bravo
AF:
0.417
TwinsUK
AF:
0.234
AC:
866
ALSPAC
AF:
0.226
AC:
872
ESP6500AA
AF:
0.708
AC:
3119
ESP6500EA
AF:
0.222
AC:
1909
ExAC
AF:
0.320
AC:
38882
Asia WGS
AF:
0.432
AC:
1502
AN:
3478
EpiCase
AF:
0.227
EpiControl
AF:
0.231

ClinVar

Significance: Benign
Submissions summary: Benign:12Other:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

Basal laminar drusen Benign:3
Benign, criteria provided, single submitterclinical testingIllumina Laboratory Services, IlluminaApr 27, 2017This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases was too high to be consistent with this variant causing disease. Therefore, this variant is classified as benign. -
Benign, criteria provided, single submitterclinical testingMendelicsMay 28, 2019- -
Benign, criteria provided, single submitterclinical testingGenome-Nilou LabJul 22, 2021- -
not provided Benign:2Other:1
Benign, criteria provided, single submitterclinical testingGeneDxMay 04, 2021This variant is associated with the following publications: (PMID: 21106043, 25087612, 20538655, 23274582, 18340363, 19549636, 18421087, 20574013, 24722444, 21270465, 24550392, 22509112, 23441108, 20132989, 19187823, 21397333, 21555552, 16299065, 29686068, 28173125) -
not provided, no assertion providednot providedDepartment of Ophthalmology and Visual Sciences Kyoto University-- -
Benign, criteria provided, single submitterclinical testingInvitaeNov 03, 2022- -
Age related macular degeneration 4 Benign:2Other:1
risk factor, no assertion criteria providedliterature onlyOMIMSep 11, 2011- -
Benign, criteria provided, single submitterclinical testingIllumina Laboratory Services, IlluminaApr 27, 2017This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). Publications were found based on this search. The evidence from the literature, in combination with allele frequency data from public databases where available, was sufficient to rule this variant out of causing disease. Therefore, this variant is classified as benign. -
Benign, criteria provided, single submitterclinical testingGenome-Nilou LabJul 22, 2021- -
Hemolytic uremic syndrome, atypical, susceptibility to, 1 Benign:2
Benign, criteria provided, single submitterclinical testingIllumina Laboratory Services, IlluminaApr 27, 2017This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases was too high to be consistent with this variant causing disease. Therefore, this variant is classified as benign. -
Benign, criteria provided, single submitterclinical testingGenome-Nilou LabJul 22, 2021- -
Factor H deficiency Benign:1
Benign, criteria provided, single submitterclinical testingGenome-Nilou LabJul 22, 2021- -
CFH-Related Dense Deposit Disease / Membranoproliferative Glomerulonephritis Type II Benign:1
Benign, criteria provided, single submitterclinical testingIllumina Laboratory Services, IlluminaApr 27, 2017This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases was too high to be consistent with this variant causing disease. Therefore, this variant is classified as benign. -
Focal segmental glomerulosclerosis Benign:1
Benign, criteria provided, single submitterclinical testingGenome Diagnostics Laboratory, The Hospital for Sick ChildrenSep 27, 2022- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.059
BayesDel_addAF
Benign
-0.65
T
BayesDel_noAF
Benign
-0.57
Cadd
Benign
7.6
Dann
Benign
0.087
Eigen
Benign
-1.2
Eigen_PC
Benign
-1.0
FATHMM_MKL
Benign
0.0021
N
LIST_S2
Benign
0.36
T;T;T
MetaRNN
Benign
0.0000056
T;T;T
MetaSVM
Benign
-0.94
T
MutationTaster
Benign
1.0
P;P;P
PrimateAI
Uncertain
0.53
T
PROVEAN
Benign
0.49
N;.;N
REVEL
Benign
0.14
Sift
Benign
1.0
T;.;T
Sift4G
Benign
1.0
T;T;T
Polyphen
0.0
.;.;B
Vest4
0.10
MPC
0.11
ClinPred
0.0013
T
GERP RS
5.1
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7
gMVP
0.69

Splicing

Find out SpliceAI 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: rs800292; hg19: chr1-196642233; COSMIC: COSV62776782; COSMIC: COSV62776782;