1-196825389-C-T

Position:

• chr1-196825389-C-T

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.59-88C>T 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 1,020,500 control chromosomes in the GnomAD database, including 127,135 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.48 (21414 hom., cov: 23)
  • Exomes 𝑓: 0.43 (105721 hom.)
• Consequence: CFHR1 NM_002113.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.06

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=-0.98).
• BP6: Variant 1-196825389-C-T is Benign according to our data. Variant chr1-196825389-C-T is described in ClinVar as [Benign]. Clinvar id is 1232483.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.582 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CFHR1	NM_002113.3	c.59-88C>T		intron_variant		ENST00000320493.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CFHR1	ENST00000320493.10	c.59-88C>T		intron_variant		1	NM_002113.3	P1

Frequencies

GnomAD3 genomes AF: 0.475 AC: 63318 AN: 133216 Hom.: 21383 Cov.: 23

Gnomad AFR AF: 0.589

Gnomad AMI AF: 0.174

Gnomad AMR AF: 0.545

Gnomad ASJ AF: 0.520

Gnomad EAS AF: 0.548

Gnomad SAS AF: 0.442

Gnomad FIN AF: 0.377

Gnomad MID AF: 0.427

Gnomad NFE AF: 0.418

Gnomad OTH AF: 0.497

GnomAD4 exome AF: 0.431 AC: 382349 AN: 887166 Hom.: 105721 Cov.: 12 AF XY: 0.431 AC XY: 192275 AN XY: 446524

Gnomad4 AFR exome AF: 0.592

Gnomad4 AMR exome AF: 0.527

Gnomad4 ASJ exome AF: 0.509

Gnomad4 EAS exome AF: 0.531

Gnomad4 SAS exome AF: 0.421

Gnomad4 FIN exome AF: 0.390

Gnomad4 NFE exome AF: 0.419

Gnomad4 OTH exome AF: 0.447

GnomAD4 genome AF: 0.475 AC: 63385 AN: 133334 Hom.: 21414 Cov.: 23 AF XY: 0.476 AC XY: 30729 AN XY: 64590

Gnomad4 AFR AF: 0.589

Gnomad4 AMR AF: 0.546

Gnomad4 ASJ AF: 0.520

Gnomad4 EAS AF: 0.549

Gnomad4 SAS AF: 0.442

Gnomad4 FIN AF: 0.377

Gnomad4 NFE AF: 0.418

Gnomad4 OTH AF: 0.498

Alfa AF: 0.456 Hom.: 2257

Asia WGS AF: 0.512 AC: 1647 AN: 3220

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	-0.98
CADD	Benign	0.68
DANN	Benign	0.16

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: rs442759; hg19: chr1-196794519;