1-196825962-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+291G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00836 in 245,460 control chromosomes in the GnomAD database, including 551 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.014 (543 hom., cov: 24)
  • Exomes 𝑓: 0.0019 (8 hom.)
• Consequence: CFHR1 NM_002113.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.430

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 1-196825962-G-A is Benign according to our data. Variant chr1-196825962-G-A is described in ClinVar as [Benign]. Clinvar id is 1266371.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0525 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CFHR1	NM_002113.3	c.253+291G>A		intron_variant		ENST00000320493.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CFHR1	ENST00000320493.10	c.253+291G>A		intron_variant		1	NM_002113.3	P1

Frequencies

GnomAD3 genomes AF: 0.0136 AC: 1838 AN: 134892 Hom.: 541 Cov.: 24

Gnomad AFR AF: 0.0545

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00565

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000391

Gnomad SAS AF: 0.000255

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000934

Gnomad OTH AF: 0.0149

GnomAD4 exome AF: 0.00187 AC: 206 AN: 110454 Hom.: 8 Cov.: 0 AF XY: 0.00152 AC XY: 87 AN XY: 57272

Gnomad4 AFR exome AF: 0.0565

Gnomad4 AMR exome AF: 0.00448

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.000390

Gnomad4 SAS exome AF: 0.000256

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000316

Gnomad4 OTH exome AF: 0.00326

GnomAD4 genome AF: 0.0137 AC: 1846 AN: 135006 Hom.: 543 Cov.: 24 AF XY: 0.0138 AC XY: 907 AN XY: 65704

Gnomad4 AFR AF: 0.0546

Gnomad4 AMR AF: 0.00564

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.000392

Gnomad4 SAS AF: 0.000256

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000934

Gnomad4 OTH AF: 0.0148

Alfa AF: 0.0133 Hom.: 49

Asia WGS AF: 0.00217 AC: 7 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

Oct 07, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
Cadd	Benign	1.2
Dann	Benign	0.63

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: rs149539863; hg19: chr1-196795092;