chr1-196651923-T-C

Variant summary

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

The ENST00000359637.3(CFH):​c.-195T>C variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0252 in 591,620 control chromosomes in the GnomAD database, including 761 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.046 ( 454 hom., cov: 32)
Exomes 𝑓: 0.018 ( 307 hom. )

Consequence

CFH
ENST00000359637.3 5_prime_UTR

Scores

2

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:10

Conservation

PhyloP100: -0.652
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 Benign. Variant got -20 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.77).
BP6
Variant 1-196651923-T-C is Benign according to our data. Variant chr1-196651923-T-C is described in ClinVar as [Benign]. Clinvar id is 294473.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BA1
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.138 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
CFHENST00000359637.3 linkuse as main transcriptc.-195T>C 5_prime_UTR_variant 1/91
CFHENST00000695968.1 linkuse as main transcriptc.-195T>C 5_prime_UTR_variant 1/8
CFHENST00000695969.1 linkuse as main transcriptc.-195T>C 5_prime_UTR_variant 1/17

Frequencies

GnomAD3 genomes
AF:
0.0460
AC:
6997
AN:
152152
Hom.:
448
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.140
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.0188
Gnomad ASJ
AF:
0.000288
Gnomad EAS
AF:
0.0504
Gnomad SAS
AF:
0.0718
Gnomad FIN
AF:
0.00235
Gnomad MID
AF:
0.00316
Gnomad NFE
AF:
0.00273
Gnomad OTH
AF:
0.0392
GnomAD4 exome
AF:
0.0179
AC:
7854
AN:
439350
Hom.:
307
Cov.:
3
AF XY:
0.0197
AC XY:
4634
AN XY:
234978
show subpopulations
Gnomad4 AFR exome
AF:
0.142
Gnomad4 AMR exome
AF:
0.0111
Gnomad4 ASJ exome
AF:
0.000730
Gnomad4 EAS exome
AF:
0.0514
Gnomad4 SAS exome
AF:
0.0658
Gnomad4 FIN exome
AF:
0.00187
Gnomad4 NFE exome
AF:
0.00286
Gnomad4 OTH exome
AF:
0.0209
GnomAD4 genome
AF:
0.0462
AC:
7028
AN:
152270
Hom.:
454
Cov.:
32
AF XY:
0.0460
AC XY:
3425
AN XY:
74456
show subpopulations
Gnomad4 AFR
AF:
0.141
Gnomad4 AMR
AF:
0.0187
Gnomad4 ASJ
AF:
0.000288
Gnomad4 EAS
AF:
0.0503
Gnomad4 SAS
AF:
0.0719
Gnomad4 FIN
AF:
0.00235
Gnomad4 NFE
AF:
0.00273
Gnomad4 OTH
AF:
0.0407
Alfa
AF:
0.0137
Hom.:
59
Bravo
AF:
0.0505
Asia WGS
AF:
0.0790
AC:
274
AN:
3478

ClinVar

Significance: Benign
Submissions summary: Benign:10
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

Hemolytic uremic syndrome, atypical, susceptibility to, 1 Benign:2
Benign, criteria provided, single submitterclinical testingGenome-Nilou LabApr 11, 2023- -
Benign, criteria provided, single submitterclinical testingIllumina Laboratory Services, IlluminaJan 12, 2018This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -
not provided Benign:2
Benign, criteria provided, single submitterclinical testingGeneDxMay 11, 2021- -
Benign, criteria provided, single submitternot providedBreakthrough Genomics, Breakthrough Genomics-- -
Age related macular degeneration 4 Benign:2
Benign, criteria provided, single submitterclinical testingGenome-Nilou LabApr 11, 2023- -
Benign, criteria provided, single submitterclinical testingIllumina Laboratory Services, IlluminaJan 12, 2018This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -
Basal laminar drusen Benign:2
Benign, criteria provided, single submitterclinical testingIllumina Laboratory Services, IlluminaJan 12, 2018This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -
Benign, criteria provided, single submitterclinical testingGenome-Nilou LabApr 11, 2023- -
Factor H deficiency Benign:1
Benign, criteria provided, single submitterclinical testingGenome-Nilou LabApr 11, 2023- -
CFH-Related Dense Deposit Disease / Membranoproliferative Glomerulonephritis Type II Benign:1
Benign, criteria provided, single submitterclinical testingIllumina Laboratory Services, IlluminaJan 12, 2018This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.77
CADD
Benign
6.1
DANN
Benign
0.56

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

LitVar

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

Other links and lift over

dbSNP: rs35836460; hg19: chr1-196621053; API