rs10922153

chr1-197009485-T-G

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_030787.4(CFHR5):c.*802T>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.383 in 152,060 control chromosomes in the GnomAD database, including 12,795 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.38 (12795 hom., cov: 31)
  • Failed GnomAD Quality Control
• Consequence: CFHR5 NM_030787.4 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.55

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]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BP6: Variant 1-197009485-T-G is Benign according to our data. Variant chr1-197009485-T-G is described in ClinVar as [Benign]. Clinvar id is 294562.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.507 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CFHR5	NM_030787.4	c.*802T>G		3_prime_UTR_variant	10/10	ENST00000256785.5
CFHR5	XM_011510020.3	c.*802T>G		3_prime_UTR_variant	10/10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CFHR5	ENST00000256785.5	c.*802T>G		3_prime_UTR_variant	10/10	1	NM_030787.4	P1

Frequencies

GnomAD3 genomes AF: 0.383 AC: 58231 AN: 151942 Hom.: 12785 Cov.: 31

Gnomad AFR AF: 0.192

Gnomad AMI AF: 0.753

Gnomad AMR AF: 0.343

Gnomad ASJ AF: 0.406

Gnomad EAS AF: 0.129

Gnomad SAS AF: 0.377

Gnomad FIN AF: 0.455

Gnomad MID AF: 0.418

Gnomad NFE AF: 0.511

Gnomad OTH AF: 0.388

GnomAD4 exome Data not reliable, filtered out with message: AC0 AC: 0 AN: 0 Hom.: 0 Cov.: 0 AC XY: 0 AN XY: 0

GnomAD4 genome AF: 0.383 AC: 58252 AN: 152060 Hom.: 12795 Cov.: 31 AF XY: 0.377 AC XY: 28008 AN XY: 74306

Gnomad4 AFR AF: 0.192

Gnomad4 AMR AF: 0.343

Gnomad4 ASJ AF: 0.406

Gnomad4 EAS AF: 0.128

Gnomad4 SAS AF: 0.379

Gnomad4 FIN AF: 0.455

Gnomad4 NFE AF: 0.511

Gnomad4 OTH AF: 0.389

Alfa AF: 0.496 Hom.: 27926

Bravo AF: 0.366

Asia WGS AF: 0.253 AC: 880 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

CFH-Related Dense Deposit Disease / Membranoproliferative Glomerulonephritis Type II Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 12, 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. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
Cadd	Benign	4.6
Dann	Benign	0.55

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

Other links and lift over

dbSNP: rs10922153; hg19: chr1-196978615; COSMIC: COSV56819761;