rs438781

Positions:

• chr1-196827110-T-A
• chr1-196827110-T-C

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_002113.3(CFHR1):​c.430+105T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.437 in 1,175,806 control chromosomes in the GnomAD database, including 148,859 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.49 (22960 hom., cov: 25)
  • Exomes 𝑓: 0.43 (125899 hom.)
• Consequence: CFHR1 NM_002113.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.94

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]

CFHR1 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.97).
• BP6: Variant 1-196827110-T-A is Benign according to our data. Variant chr1-196827110-T-A is described in ClinVar as [Benign]. Clinvar id is 1290026.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.656 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CFHR1	NM_002113.3	c.430+105T>A		intron_variant		ENST00000320493.10	NP_002104.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CFHR1	ENST00000320493.10	c.430+105T>A		intron_variant		1	NM_002113.3	ENSP00000314299.5

Frequencies

GnomAD3 genomes AF: 0.493 AC: 66164 AN: 134086 Hom.: 22920 Cov.: 25

Gnomad AFR AF: 0.664

Gnomad AMI AF: 0.178

Gnomad AMR AF: 0.552

Gnomad ASJ AF: 0.524

Gnomad EAS AF: 0.548

Gnomad SAS AF: 0.438

Gnomad FIN AF: 0.378

Gnomad MID AF: 0.414

Gnomad NFE AF: 0.418

Gnomad OTH AF: 0.508

GnomAD4 exome AF: 0.429 AC: 447273 AN: 1041606 Hom.: 125899 AF XY: 0.429 AC XY: 225450 AN XY: 525726

Gnomad4 AFR exome AF: 0.663

Gnomad4 AMR exome AF: 0.531

Gnomad4 ASJ exome AF: 0.511

Gnomad4 EAS exome AF: 0.528

Gnomad4 SAS exome AF: 0.422

Gnomad4 FIN exome AF: 0.392

Gnomad4 NFE exome AF: 0.414

Gnomad4 OTH exome AF: 0.448

GnomAD4 genome AF: 0.494 AC: 66245 AN: 134200 Hom.: 22960 Cov.: 25 AF XY: 0.494 AC XY: 32263 AN XY: 65248

Gnomad4 AFR AF: 0.663

Gnomad4 AMR AF: 0.553

Gnomad4 ASJ AF: 0.524

Gnomad4 EAS AF: 0.549

Gnomad4 SAS AF: 0.439

Gnomad4 FIN AF: 0.378

Gnomad4 NFE AF: 0.418

Gnomad4 OTH AF: 0.508

Alfa AF: 0.477 Hom.: 2524

Asia WGS AF: 0.517 AC: 1672 AN: 3236

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Jul 09, 2018	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	0.47
DANN	Benign	0.36

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: rs438781; hg19: chr1-196796240; COSMIC: COSV57626532; COSMIC: COSV57626532;