1-196688525-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_000186.4(CFH):​c.965-895C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.645 in 151,972 control chromosomes in the GnomAD database, including 32,036 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.64 ( 32036 hom., cov: 32)

Consequence

CFH
NM_000186.4 intron

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.492
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 -12 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-1.03).
BA1
GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.926 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
CFHNM_000186.4 linkc.965-895C>T intron_variant Intron 7 of 21 ENST00000367429.9 NP_000177.2 P08603A0A024R962
CFHNM_001014975.3 linkc.965-895C>T intron_variant Intron 7 of 9 NP_001014975.1 A0A0D9SG88

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
CFHENST00000367429.9 linkc.965-895C>T intron_variant Intron 7 of 21 1 NM_000186.4 ENSP00000356399.4 P08603
ENSG00000289697ENST00000696032.1 linkc.965-895C>T intron_variant Intron 7 of 26 ENSP00000512341.1 A0A8Q3SIA1

Frequencies

GnomAD3 genomes
AF:
0.645
AC:
97919
AN:
151854
Hom.:
32012
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.629
Gnomad AMI
AF:
0.521
Gnomad AMR
AF:
0.737
Gnomad ASJ
AF:
0.662
Gnomad EAS
AF:
0.948
Gnomad SAS
AF:
0.719
Gnomad FIN
AF:
0.564
Gnomad MID
AF:
0.668
Gnomad NFE
AF:
0.618
Gnomad OTH
AF:
0.666
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome
AF:
0.645
AC:
97984
AN:
151972
Hom.:
32036
Cov.:
32
AF XY:
0.648
AC XY:
48099
AN XY:
74258
show subpopulations
Gnomad4 AFR
AF:
0.629
Gnomad4 AMR
AF:
0.737
Gnomad4 ASJ
AF:
0.662
Gnomad4 EAS
AF:
0.949
Gnomad4 SAS
AF:
0.720
Gnomad4 FIN
AF:
0.564
Gnomad4 NFE
AF:
0.618
Gnomad4 OTH
AF:
0.665
Alfa
AF:
0.629
Hom.:
3754
Bravo
AF:
0.660
Asia WGS
AF:
0.780
AC:
2707
AN:
3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-1.0
CADD
Benign
1.4
DANN
Benign
0.63

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: rs10801554; hg19: chr1-196657655; API