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rs1410996

Variant summary

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

The NM_000186.4(CFH):c.2237-543G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.459 in 152,002 control chromosomes in the GnomAD database, including 16,344 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 0.46 ( 16344 hom., cov: 33)

Consequence

CFH
NM_000186.4 intron

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.24
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.93).
BA1
GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.541 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
CFHNM_000186.4 linkuse as main transcriptc.2237-543G>A intron_variant ENST00000367429.9

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
CFHENST00000367429.9 linkuse as main transcriptc.2237-543G>A intron_variant 1 NM_000186.4 P2

Frequencies

GnomAD3 genomes
AF:
0.459
AC:
69713
AN:
151884
Hom.:
16321
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.532
Gnomad AMI
AF:
0.258
Gnomad AMR
AF:
0.496
Gnomad ASJ
AF:
0.522
Gnomad EAS
AF:
0.441
Gnomad SAS
AF:
0.559
Gnomad FIN
AF:
0.400
Gnomad MID
AF:
0.453
Gnomad NFE
AF:
0.408
Gnomad OTH
AF:
0.479
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome
AF:
0.459
AC:
69778
AN:
152002
Hom.:
16344
Cov.:
33
AF XY:
0.464
AC XY:
34477
AN XY:
74312
show subpopulations
Gnomad4 AFR
AF:
0.532
Gnomad4 AMR
AF:
0.497
Gnomad4 ASJ
AF:
0.522
Gnomad4 EAS
AF:
0.441
Gnomad4 SAS
AF:
0.559
Gnomad4 FIN
AF:
0.400
Gnomad4 NFE
AF:
0.408
Gnomad4 OTH
AF:
0.481
Alfa
AF:
0.403
Hom.:
25050
Bravo
AF:
0.466
Asia WGS
AF:
0.532
AC:
1847
AN:
3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.93
Cadd
Benign
0.18
Dann
Benign
0.43

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: rs1410996; hg19: chr1-196696933; API