Variant 1-196982740-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_030787.4(CFHR5):c.59-145A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00561 in 721,134 control chromosomes in the GnomAD database, including 126 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.019 ( 90 hom., cov: 32)

Exomes 𝑓: 0.0021 ( 36 hom. )

Consequence

CFHR5
NM_030787.4 intron

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -1.58

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.95).

BP6

Variant 1-196982740-A-G is Benign according to our data. Variant chr1-196982740-A-G is described in ClinVar as [Benign]. Clinvar id is 1222004.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0623 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.59-145A>G		intron_variant		ENST00000256785.5
CFHR5	XM_011510020.3 linkuse as main transcript	c.68-145A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	MANE	Appris
CFHR5	ENST00000256785.5 linkuse as main transcript	c.59-145A>G	intron_variant	1	NM_030787.4	P1
CFHR5	ENST00000699466.1 linkuse as main transcript	c.-197-145A>G	intron_variant
CFHR5	ENST00000699468.1 linkuse as main transcript	c.-25+5060A>G	intron_variant
CFHR5	ENST00000699467.1 linkuse as main transcript	n.128-145A>G	intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes

AF:

0.0187

AC:

2844

AN:

152168

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0646

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00845

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000176

Gnomad OTH

AF:

0.0124

GnomAD4 exome

AF:

0.00212

AC:

1207

AN:

568848

Hom.:

AF XY:

0.00169

AC XY:

514

AN XY:

304476

show subpopulations

Gnomad4 AFR exome

AF:

0.0640

Gnomad4 AMR exome

AF:

0.00409

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000910

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000914

Gnomad4 OTH exome

AF:

0.00417

GnomAD4 genome

AF:

0.0187

AC:

2841

AN:

152286

Hom.:

Cov.:

AF XY:

0.0171

AC XY:

1274

AN XY:

74452

show subpopulations

Gnomad4 AFR

AF:

0.0644

Gnomad4 AMR

AF:

0.00843

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000176

Gnomad4 OTH

AF:

0.0123

Alfa

AF:

0.0146

Hom.:

Bravo

AF:

0.0217

Asia WGS

AF:

0.00404

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 19, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.95

CADD

Benign

0.016

DANN

Benign

0.61

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