1-196977645-T-C

Position:

chr1-196977645-T-C

Variant summary

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

The NM_030787.4(CFHR5):c.-20T>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 0.107 in 1,596,032 control chromosomes in the GnomAD database, including 14,105 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.18 ( 4380 hom., cov: 32)

Exomes 𝑓: 0.099 ( 9725 hom. )

Consequence

CFHR5
NM_030787.4 5_prime_UTR

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: 0.00400

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]

CFHR5 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.93).

BP6

Variant 1-196977645-T-C is Benign according to our data. Variant chr1-196977645-T-C is described in ClinVar as [Benign]. Clinvar id is 294531.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr1-196977645-T-C is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.428 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CFHR5	NM_030787.4 linkuse as main transcript	c.-20T>C		5_prime_UTR_variant	1/10	ENST00000256785.5
CFHR5	XM_011510020.3 linkuse as main transcript	c.67+2531T>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	Effect	#exon/exons	TSL	MANE	Appris
CFHR5	ENST00000256785.5 linkuse as main transcript	c.-20T>C	5_prime_UTR_variant	1/10	1	NM_030787.4	P1
CFHR5	ENST00000699468.1 linkuse as main transcript	c.-60T>C	5_prime_UTR_variant	1/6
CFHR5	ENST00000699466.1 linkuse as main transcript	c.-198+2531T>C	intron_variant
CFHR5	ENST00000699467.1 linkuse as main transcript	n.127+2057T>C	intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes

AF:

0.182

AC:

27729

AN:

151990

Hom.:

4374

Cov.:

show subpopulations

Gnomad AFR

AF:

0.434

Gnomad AMI

AF:

0.0450

Gnomad AMR

AF:

0.114

Gnomad ASJ

AF:

0.0862

Gnomad EAS

AF:

0.000770

Gnomad SAS

AF:

0.101

Gnomad FIN

AF:

0.0714

Gnomad MID

AF:

0.114

Gnomad NFE

AF:

0.0896

Gnomad OTH

AF:

0.165

GnomAD3 exomes

AF:

0.103

AC:

25922

AN:

251402

Hom.:

2491

AF XY:

0.0989

AC XY:

13441

AN XY:

135870

show subpopulations

Gnomad AFR exome

AF:

0.436

Gnomad AMR exome

AF:

0.0589

Gnomad ASJ exome

AF:

0.0928

Gnomad EAS exome

AF:

0.000217

Gnomad SAS exome

AF:

0.101

Gnomad FIN exome

AF:

0.0698

Gnomad NFE exome

AF:

0.0939

Gnomad OTH exome

AF:

0.0952

GnomAD4 exome

AF:

0.0989

AC:

142789

AN:

1443924

Hom.:

9725

Cov.:

AF XY:

0.0982

AC XY:

70659

AN XY:

719706

show subpopulations

Gnomad4 AFR exome

AF:

0.442

Gnomad4 AMR exome

AF:

0.0635

Gnomad4 ASJ exome

AF:

0.0864

Gnomad4 EAS exome

AF:

0.000253

Gnomad4 SAS exome

AF:

0.100

Gnomad4 FIN exome

AF:

0.0676

Gnomad4 NFE exome

AF:

0.0947

Gnomad4 OTH exome

AF:

0.108

GnomAD4 genome

AF:

0.182

AC:

27754

AN:

152108

Hom.:

4380

Cov.:

AF XY:

0.180

AC XY:

13346

AN XY:

74338

show subpopulations

Gnomad4 AFR

AF:

0.433

Gnomad4 AMR

AF:

0.114

Gnomad4 ASJ

AF:

0.0862

Gnomad4 EAS

AF:

0.000772

Gnomad4 SAS

AF:

0.100

Gnomad4 FIN

AF:

0.0714

Gnomad4 NFE

AF:

0.0896

Gnomad4 OTH

AF:

0.164

Alfa

AF:

0.110

Hom.:

2350

Bravo

AF:

0.196

Asia WGS

AF:

0.0710

AC:

246

AN:

3478

EpiCase

AF:

0.0939

EpiControl

AF:

0.0898

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Nov 11, 2018	This variant is associated with the following publications: (PMID: 21784901, 16299065) -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

CFH-Related Dense Deposit Disease / Membranoproliferative Glomerulonephritis Type II

Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Mar 06, 2018

This 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. -

CFHR5 deficiency

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Apr 11, 2023

- -

Atypical hemolytic-uremic syndrome

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome Diagnostics Laboratory, The Hospital for Sick Children

Oct 05, 2022

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.93

CADD

Benign

3.8

DANN

Benign

0.79

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over