1-196825884-G-A

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.253+213G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.462 in 440,456 control chromosomes in the GnomAD database, including 59,863 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.49 (22767 hom., cov: 23)
  • Exomes 𝑓: 0.45 (37096 hom.)
• Consequence: CFHR1 NM_002113.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.213

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=-1.03).
• BP6: Variant 1-196825884-G-A is Benign according to our data. Variant chr1-196825884-G-A is described in ClinVar as [Benign]. Clinvar id is 1278665.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.655 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CFHR1	NM_002113.3	c.253+213G>A		intron_variant		ENST00000320493.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CFHR1	ENST00000320493.10	c.253+213G>A		intron_variant		1	NM_002113.3	P1

Frequencies

GnomAD3 genomes AF: 0.493 AC: 65784 AN: 133344 Hom.: 22725 Cov.: 23

Gnomad AFR AF: 0.663

Gnomad AMI AF: 0.175

Gnomad AMR AF: 0.554

Gnomad ASJ AF: 0.518

Gnomad EAS AF: 0.548

Gnomad SAS AF: 0.445

Gnomad FIN AF: 0.379

Gnomad MID AF: 0.423

Gnomad NFE AF: 0.417

Gnomad OTH AF: 0.513

GnomAD4 exome AF: 0.449 AC: 137774 AN: 306996 Hom.: 37096 Cov.: 4 AF XY: 0.448 AC XY: 71776 AN XY: 160238

Gnomad4 AFR exome AF: 0.673

Gnomad4 AMR exome AF: 0.552

Gnomad4 ASJ exome AF: 0.514

Gnomad4 EAS exome AF: 0.538

Gnomad4 SAS exome AF: 0.433

Gnomad4 FIN exome AF: 0.406

Gnomad4 NFE exome AF: 0.423

Gnomad4 OTH exome AF: 0.467

GnomAD4 genome AF: 0.494 AC: 65869 AN: 133460 Hom.: 22767 Cov.: 23 AF XY: 0.494 AC XY: 32037 AN XY: 64816

Gnomad4 AFR AF: 0.663

Gnomad4 AMR AF: 0.554

Gnomad4 ASJ AF: 0.518

Gnomad4 EAS AF: 0.549

Gnomad4 SAS AF: 0.447

Gnomad4 FIN AF: 0.379

Gnomad4 NFE AF: 0.417

Gnomad4 OTH AF: 0.514

Alfa AF: 0.209 Hom.: 488

Asia WGS AF: 0.516 AC: 1668 AN: 3236

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

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
Cadd	Benign	2.0
Dann	Benign	0.52

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: rs409253; hg19: chr1-196795014;