chr1-197004053-T-C

Variant summary

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

The NM_030787.4(CFHR5):​c.1331-608T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.197 in 152,094 control chromosomes in the GnomAD database, including 4,158 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 0.20 ( 4158 hom., cov: 32)

Consequence

CFHR5
NM_030787.4 intron

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.215
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=-0.95).
BA1
GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.671 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
CFHR5NM_030787.4 linkuse as main transcriptc.1331-608T>C intron_variant ENST00000256785.5
CFHR5XM_011510020.3 linkuse as main transcriptc.1340-608T>C intron_variant

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
CFHR5ENST00000256785.5 linkuse as main transcriptc.1331-608T>C intron_variant 1 NM_030787.4 P1

Frequencies

GnomAD3 genomes
AF:
0.197
AC:
29925
AN:
151976
Hom.:
4148
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.115
Gnomad AMI
AF:
0.0647
Gnomad AMR
AF:
0.343
Gnomad ASJ
AF:
0.188
Gnomad EAS
AF:
0.690
Gnomad SAS
AF:
0.323
Gnomad FIN
AF:
0.249
Gnomad MID
AF:
0.123
Gnomad NFE
AF:
0.162
Gnomad OTH
AF:
0.203
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome
AF:
0.197
AC:
29946
AN:
152094
Hom.:
4158
Cov.:
32
AF XY:
0.208
AC XY:
15493
AN XY:
74334
show subpopulations
Gnomad4 AFR
AF:
0.115
Gnomad4 AMR
AF:
0.344
Gnomad4 ASJ
AF:
0.188
Gnomad4 EAS
AF:
0.690
Gnomad4 SAS
AF:
0.322
Gnomad4 FIN
AF:
0.249
Gnomad4 NFE
AF:
0.162
Gnomad4 OTH
AF:
0.204
Alfa
AF:
0.160
Hom.:
2202
Bravo
AF:
0.203
Asia WGS
AF:
0.495
AC:
1716
AN:
3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.95
CADD
Benign
4.4
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: rs12116643; hg19: chr1-196973183; API