1-196977739-T-A

Variant names:

Variant summary

Our verdict is Benign. The variant received -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

Publications

7 publications found

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 Gene-Disease associations (from GenCC):

C3 glomerulonephritis
Inheritance: AD Classification: STRONG, MODERATE Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae)

CFHR5 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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.

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 rank	MANE	Protein	UniProt
CFHR5	NM_030787.4 link	c.58+17T>A		intron_variant	Intron 1 of 9	ENST00000256785.5	NP_110414.1	Q9BXR6
CFHR5	XM_011510020.3 link	c.67+2625T>A		intron_variant	Intron 1 of 9		XP_011508322.1

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
CFHR5	ENST00000256785.5 link	c.58+17T>A	intron_variant	Intron 1 of 9	1	NM_030787.4	ENSP00000256785.4	Q9BXR6
CFHR5	ENST00000699466.1 link	c.-198+2625T>A	intron_variant	Intron 1 of 9			ENSP00000514393.1	A0A8V8TNA3
CFHR5	ENST00000699468.1 link	c.-25+59T>A	intron_variant	Intron 1 of 5			ENSP00000514394.1	A0A8V8TNF4
CFHR5	ENST00000699467.1 link	n.127+2151T>A	intron_variant	Intron 1 of 9

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

GnomAD2 exomes

AF:

0.206

AC:

51752

AN:

251352

AF XY:

0.212

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 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

African (AFR)

AF:

0.0669

AC:

2204

AN:

32966

American (AMR)

AF:

0.148

AC:

6601

AN:

44682

Ashkenazi Jewish (ASJ)

AF:

0.283

AC:

7352

AN:

25944

East Asian (EAS)

AF:

0.154

AC:

6086

AN:

39496

South Asian (SAS)

AF:

0.209

AC:

17907

AN:

85512

European-Finnish (FIN)

AF:

0.214

AC:

11438

AN:

53370

Middle Eastern (MID)

AF:

0.250

AC:

1426

AN:

5704

European-Non Finnish (NFE)

AF:

0.227

AC:

246266

AN:

1086126

Other (OTH)

AF:

0.213

AC:

12655

AN:

59360

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.466

Heterozygous variant carriers

10494

20989

31483

41978

52472

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.182

AC:

27720

AN:

152126

Hom.:

2931

Cov.:

AF XY:

0.182

AC XY:

13543

AN XY:

74364

show subpopulations

African (AFR)

AF:

0.0756

AC:

3142

AN:

41538

American (AMR)

AF:

0.179

AC:

2738

AN:

15278

Ashkenazi Jewish (ASJ)

AF:

0.292

AC:

1011

AN:

3468

East Asian (EAS)

AF:

0.158

AC:

818

AN:

5168

South Asian (SAS)

AF:

0.200

AC:

957

AN:

4796

European-Finnish (FIN)

AF:

0.222

AC:

2351

AN:

10584

Middle Eastern (MID)

AF:

0.340

AC:

100

AN:

294

European-Non Finnish (NFE)

AF:

0.236

AC:

16044

AN:

67976

Other (OTH)

AF:

0.206

AC:

435

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1130

2260

3390

4520

5650

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

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

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Nov 10, 2018

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

CFHR5 deficiency

Benign:1

Apr 11, 2023

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.88

CADD

Benign

5.7

(source)

DANN

Benign

0.63

PhyloP100

-0.26

PromoterAI

-0.00040

Neutral

(source)

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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1-196977739-T-A

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over