Variant 1-196977739-T-A details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_030787.4(CFHR5):c.58+17T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.214 in 1,585,286 control chromosomes in the GnomAD database, including 38,437 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.18 ( 2931 hom., cov: 32)

Exomes 𝑓: 0.22 ( 35506 hom. )

Consequence

CFHR5
NM_030787.4 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: -0.264

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=-0.88).

BP6

Variant 1-196977739-T-A is Benign according to our data. Variant chr1-196977739-T-A is described in ClinVar as [Benign]. Clinvar id is 1273904.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr1-196977739-T-A is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.233 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.58+17T>A		intron_variant		ENST00000256785.5
CFHR5	XM_011510020.3 linkuse as main transcript	c.67+2625T>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	MANE	Appris
CFHR5	ENST00000256785.5 linkuse as main transcript	c.58+17T>A	intron_variant	1	NM_030787.4	P1
CFHR5	ENST00000699466.1 linkuse as main transcript	c.-198+2625T>A	intron_variant
CFHR5	ENST00000699468.1 linkuse as main transcript	c.-25+59T>A	intron_variant
CFHR5	ENST00000699467.1 linkuse as main transcript	n.127+2151T>A	intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes

AF:

0.182

AC:

27724

AN:

152010

Hom.:

2934

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0757

Gnomad AMI

AF:

0.136

Gnomad AMR

AF:

0.180

Gnomad ASJ

AF:

0.292

Gnomad EAS

AF:

0.158

Gnomad SAS

AF:

0.200

Gnomad FIN

AF:

0.222

Gnomad MID

AF:

0.339

Gnomad NFE

AF:

0.236

Gnomad OTH

AF:

0.206

GnomAD3 exomes

AF:

0.206

AC:

51752

AN:

251352

Hom.:

5798

AF XY:

0.212

AC XY:

28842

AN XY:

135852

show subpopulations

Gnomad AFR exome

AF:

0.0738

Gnomad AMR exome

AF:

0.144

Gnomad ASJ exome

AF:

0.287

Gnomad EAS exome

AF:

0.167

Gnomad SAS exome

AF:

0.212

Gnomad FIN exome

AF:

0.214

Gnomad NFE exome

AF:

0.239

Gnomad OTH exome

AF:

0.221

GnomAD4 exome

AF:

0.218

AC:

311935

AN:

1433160

Hom.:

35506

Cov.:

AF XY:

0.219

AC XY:

156433

AN XY:

714924

show subpopulations

Gnomad4 AFR exome

AF:

0.0669

Gnomad4 AMR exome

AF:

0.148

Gnomad4 ASJ exome

AF:

0.283

Gnomad4 EAS exome

AF:

0.154

Gnomad4 SAS exome

AF:

0.209

Gnomad4 FIN exome

AF:

0.214

Gnomad4 NFE exome

AF:

0.227

Gnomad4 OTH exome

AF:

0.213

GnomAD4 genome

AF:

0.182

AC:

27720

AN:

152126

Hom.:

2931

Cov.:

AF XY:

0.182

AC XY:

13543

AN XY:

74364

show subpopulations

Gnomad4 AFR

AF:

0.0756

Gnomad4 AMR

AF:

0.179

Gnomad4 ASJ

AF:

0.292

Gnomad4 EAS

AF:

0.158

Gnomad4 SAS

AF:

0.200

Gnomad4 FIN

AF:

0.222

Gnomad4 NFE

AF:

0.236

Gnomad4 OTH

AF:

0.206

Alfa

AF:

0.192

Hom.:

1922

Bravo

AF:

0.173

Asia WGS

AF:

0.161

AC:

562

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 30, 2024	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Nov 10, 2018	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

CFHR5 deficiency

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Apr 11, 2023

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.88

CADD

Benign

5.7

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.

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