rs1750311

Variant summary

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

The NM_030787.4(CFHR5):​c.430+958C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.418 in 151,882 control chromosomes in the GnomAD database, including 15,509 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 0.42 ( 15509 hom., cov: 32)

Consequence

CFHR5
NM_030787.4 intron

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.59
Variant links:
Genes affected
CFHR5 (HGNC:24668): (complement factor H related 5) This gene is a member of a small complement factor H (CFH) gene cluster on chromosome 1. Each member of this gene family contains multiple short consensus repeats (SCRs) typical of regulators of complement activation. The protein encoded by this gene has nine SCRs with the first two repeats having heparin binding properties, a region within repeats 5-7 having heparin binding and C reactive protein binding properties, and the C-terminal repeats being similar to a complement component 3 b (C3b) binding domain. This protein co-localizes with C3, binds C3b in a dose-dependent manner, and is recruited to tissues damaged by C-reactive protein. Allelic variations in this gene have been associated, but not causally linked, with two different forms of kidney disease: membranoproliferative glomerulonephritis type II (MPGNII) and hemolytic uraemic syndrome (HUS). [provided by RefSeq, Jan 2010]

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=-0.98).
BA1
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.681 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
CFHR5NM_030787.4 linkuse as main transcriptc.430+958C>A intron_variant ENST00000256785.5 NP_110414.1 Q9BXR6
CFHR5XM_011510020.3 linkuse as main transcriptc.439+958C>A intron_variant XP_011508322.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
CFHR5ENST00000256785.5 linkuse as main transcriptc.430+958C>A intron_variant 1 NM_030787.4 ENSP00000256785.4 Q9BXR6
CFHR5ENST00000699466.1 linkuse as main transcriptc.175+958C>A intron_variant ENSP00000514393.1 A0A8V8TNA3
CFHR5ENST00000699468.1 linkuse as main transcriptc.-25+7415C>A intron_variant ENSP00000514394.1 A0A8V8TNF4
CFHR5ENST00000699467.1 linkuse as main transcriptn.499+958C>A intron_variant

Frequencies

GnomAD3 genomes
AF:
0.418
AC:
63444
AN:
151764
Hom.:
15475
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.687
Gnomad AMI
AF:
0.181
Gnomad AMR
AF:
0.313
Gnomad ASJ
AF:
0.406
Gnomad EAS
AF:
0.180
Gnomad SAS
AF:
0.302
Gnomad FIN
AF:
0.295
Gnomad MID
AF:
0.459
Gnomad NFE
AF:
0.327
Gnomad OTH
AF:
0.408
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome
AF:
0.418
AC:
63519
AN:
151882
Hom.:
15509
Cov.:
32
AF XY:
0.413
AC XY:
30611
AN XY:
74198
show subpopulations
Gnomad4 AFR
AF:
0.688
Gnomad4 AMR
AF:
0.312
Gnomad4 ASJ
AF:
0.406
Gnomad4 EAS
AF:
0.181
Gnomad4 SAS
AF:
0.301
Gnomad4 FIN
AF:
0.295
Gnomad4 NFE
AF:
0.327
Gnomad4 OTH
AF:
0.406
Alfa
AF:
0.330
Hom.:
14437
Bravo
AF:
0.429
Asia WGS
AF:
0.252
AC:
876
AN:
3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.98
CADD
Benign
0.71
DANN
Benign
0.68

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.010
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: rs1750311; hg19: chr1-196954225; API