1-196820031-C-G

Variant summary

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

The NM_002113.3(CFHR1):c.58+129C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.18 in 363,646 control chromosomes in the GnomAD database, including 7,002 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.21 (3278 hom., cov: 19)
  • Exomes 𝑓: 0.18 (7002 hom.)
  • Failed GnomAD Quality Control
• Consequence: CFHR1 NM_002113.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.36

Genes affected

CFHR1 (HGNC:4888): (complement factor H related 1) This gene encodes a secreted protein belonging to the complement factor H protein family. It binds to Pseudomonas aeruginosa elongation factor Tuf together with plasminogen, which is proteolytically activated. It is proposed that Tuf acts as a virulence factor by acquiring host proteins to the pathogen surface, controlling complement, and facilitating tissue invasion. Mutations in this gene are associated with an increased risk of atypical hemolytic-uremic syndrome. [provided by RefSeq, Oct 2009]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.96).
• BP6: Variant 1-196820031-C-G is Benign according to our data. Variant chr1-196820031-C-G is described in ClinVar as [Benign]. Clinvar id is 1284207.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAdExome4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.309 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CFHR1	NM_002113.3	c.58+129C>G		intron_variant		ENST00000320493.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CFHR1	ENST00000320493.10	c.58+129C>G		intron_variant		1	NM_002113.3	P1

Frequencies

GnomAD3 genomes AF: 0.207 AC: 28231 AN: 136404 Hom.: 3272 Cov.: 19

Gnomad AFR AF: 0.308

Gnomad AMI AF: 0.165

Gnomad AMR AF: 0.155

Gnomad ASJ AF: 0.187

Gnomad EAS AF: 0.00938

Gnomad SAS AF: 0.163

Gnomad FIN AF: 0.138

Gnomad MID AF: 0.168

Gnomad NFE AF: 0.193

Gnomad OTH AF: 0.219

GnomAD4 exome AF: 0.180 AC: 65278 AN: 363646 Hom.: 7002 AF XY: 0.180 AC XY: 34713 AN XY: 192414

Gnomad4 AFR exome AF: 0.319

Gnomad4 AMR exome AF: 0.134

Gnomad4 ASJ exome AF: 0.188

Gnomad4 EAS exome AF: 0.00505

Gnomad4 SAS exome AF: 0.193

Gnomad4 FIN exome AF: 0.146

Gnomad4 NFE exome AF: 0.197

Gnomad4 OTH exome AF: 0.189

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.207 AC: 28270 AN: 136518 Hom.: 3278 Cov.: 19 AF XY: 0.203 AC XY: 13364 AN XY: 65962

Gnomad4 AFR AF: 0.308

Gnomad4 AMR AF: 0.154

Gnomad4 ASJ AF: 0.187

Gnomad4 EAS AF: 0.00940

Gnomad4 SAS AF: 0.163

Gnomad4 FIN AF: 0.138

Gnomad4 NFE AF: 0.193

Gnomad4 OTH AF: 0.217

Alfa AF: 0.0629 Hom.: 69

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jul 09, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
Cadd	Benign	1.1
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: rs9427632; hg19: chr1-196789161; COSMIC: COSV57626710;