1-196825319-G-GT

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_002113.3(CFHR1):c.59-158_59-157insT variant causes a intron change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.49 (22494 hom., cov: 0)
  • Exomes 𝑓: 0.43 (50311 hom.)
• Consequence: CFHR1 NM_002113.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.615

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 -10 ACMG points.

• BP6: Variant 1-196825319-G-GT is Benign according to our data. Variant chr1-196825319-G-GT is described in ClinVar as [Benign]. Clinvar id is 1221226.Status of the report is criteria_provided_single_submitter, 1 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	UniProt
CFHR1	NM_002113.3	c.59-158_59-157insT		intron_variant		ENST00000320493.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CFHR1	ENST00000320493.10	c.59-158_59-157insT		intron_variant		1	NM_002113.3	P1

Frequencies

GnomAD3 genomes AF: 0.492 AC: 65219 AN: 132432 Hom.: 22452 Cov.: 0

Gnomad AFR AF: 0.664

Gnomad AMI AF: 0.172

Gnomad AMR AF: 0.553

Gnomad ASJ AF: 0.522

Gnomad EAS AF: 0.543

Gnomad SAS AF: 0.439

Gnomad FIN AF: 0.378

Gnomad MID AF: 0.422

Gnomad NFE AF: 0.416

Gnomad OTH AF: 0.513

GnomAD4 exome AF: 0.431 AC: 174587 AN: 405282 Hom.: 50311 Cov.: 5 AF XY: 0.429 AC XY: 91545 AN XY: 213456

Gnomad4 AFR exome AF: 0.661

Gnomad4 AMR exome AF: 0.534

Gnomad4 ASJ exome AF: 0.501

Gnomad4 EAS exome AF: 0.530

Gnomad4 SAS exome AF: 0.416

Gnomad4 FIN exome AF: 0.386

Gnomad4 NFE exome AF: 0.408

Gnomad4 OTH exome AF: 0.451

GnomAD4 genome AF: 0.493 AC: 65304 AN: 132560 Hom.: 22494 Cov.: 0 AF XY: 0.492 AC XY: 31660 AN XY: 64290

Gnomad4 AFR AF: 0.663

Gnomad4 AMR AF: 0.553

Gnomad4 ASJ AF: 0.522

Gnomad4 EAS AF: 0.544

Gnomad4 SAS AF: 0.440

Gnomad4 FIN AF: 0.378

Gnomad4 NFE AF: 0.416

Gnomad4 OTH AF: 0.514

Alfa AF: 0.476 Hom.: 2490

Asia WGS AF: 0.512 AC: 1644 AN: 3210

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

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: rs11393029; hg19: chr1-196794449;