chr1-196819862-TG-T

Position:

• chr1-196819862-TG-T

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BP6 BS1

The NM_002113.3(CFHR1):​c.19delG​(p.Val7fs) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

• Frequency:
  • Genomes: 𝑓 0.0073 (1 hom., cov: 8)
  • Exomes 𝑓: 0.00090 (0 hom.)
• Consequence: CFHR1 NM_002113.3 frameshift
• Clinical Significance: Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:2 B:1
• Conservation: PhyloP100: 0.231

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 Likely_benign. Variant got -5 ACMG points.

• BP6: Variant 1-196819862-TG-T is Benign according to our data. Variant chr1-196819862-TG-T is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 1678086.We mark this variant Likely_benign, oryginal submissions are: {Uncertain_significance=2, Likely_benign=1}.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00727 (445/61208) while in subpopulation AFR AF= 0.026 (419/16100). AF 95% confidence interval is 0.024. There are 1 homozygotes in gnomad4. There are 217 alleles in male gnomad4 subpopulation. Median coverage is 8. This position pass quality control queck.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CFHR1	NM_002113.3	c.19delG	p.Val7fs	frameshift_variant	1/6	ENST00000320493.10	NP_002104.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CFHR1	ENST00000320493.10	c.19delG	p.Val7fs	frameshift_variant	1/6	1	NM_002113.3	ENSP00000314299.5

Frequencies

GnomAD3 genomes AF: 0.00722 AC: 441 AN: 61104 Hom.: 1 Cov.: 8

Gnomad AFR AF: 0.0259

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00342

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00556

Gnomad NFE AF: 0.000126

Gnomad OTH AF: 0.00554

GnomAD4 exome AF: 0.000898 AC: 359 AN: 399986 Hom.: 0 Cov.: 4 AF XY: 0.000748 AC XY: 158 AN XY: 211354

Gnomad4 AFR exome AF: 0.0236

Gnomad4 AMR exome AF: 0.00125

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000773

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000135

Gnomad4 OTH exome AF: 0.00221

GnomAD4 genome AF: 0.00727 AC: 445 AN: 61208 Hom.: 1 Cov.: 8 AF XY: 0.00784 AC XY: 217 AN XY: 27662

Gnomad4 AFR AF: 0.0260

Gnomad4 AMR AF: 0.00341

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000126

Gnomad4 OTH AF: 0.00545

Alfa AF: 0.00446 Hom.: 0

ClinVar

Significance: Conflicting classifications of pathogenicity

Submissions summary: Uncertain:2 Benign:1

Revision: criteria provided, conflicting classifications

Submissions by phenotype

not provided Uncertain:1 Benign:1

Likely benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Dec 01, 2022	CFHR1: BS1 -
Uncertain significance, criteria provided, single submitter	clinical testing	AiLife Diagnostics, AiLife Diagnostics	Mar 30, 2022	- -

Age related macular degeneration 1;C2749604:Hemolytic uremic syndrome, atypical, susceptibility to, 1 Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Fulgent Genetics, Fulgent Genetics

Apr 06, 2022

- -

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: rs769938205; hg19: chr1-196788992;