1-196828162-G-T

Variant names:

• chr1-196828162-G-T
• rs388862
• NM_002113.3:c.523G>T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 0P and 0B.

The NM_002113.3(CFHR1):​c.523G>T​(p.Glu175*) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Variant results in nonsense mediated mRNA decay.

• Frequency:
  • Genomes: not found (cov: 12)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: CFHR1 NM_002113.3 stop_gained
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0750
• Publications: 14 publications found

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 Gene-Disease associations (from GenCC):

• dense deposit disease

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
• age related macular degeneration 1

  Inheritance: Unknown Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae)
• hemolytic uremic syndrome, atypical, susceptibility to, 1

  Inheritance: Unknown, AD Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002113.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CFHR1	NM_002113.3	MANE Select	c.523G>T	p.Glu175*	stop_gained	Exon 4 of 6	NP_002104.2
	CFHR1	NM_001379306.1		c.472G>T	p.Glu158*	stop_gained	Exon 4 of 6	NP_001366235.1
	CFHR1	NM_001379307.1		c.361G>T	p.Glu121*	stop_gained	Exon 4 of 6	NP_001366236.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CFHR1	ENST00000320493.10	TSL:1 MANE Select	c.523G>T	p.Glu175*	stop_gained	Exon 4 of 6	ENSP00000314299.5
	CFHR1	ENST00000699454.1		c.361G>T	p.Glu121*	stop_gained	Exon 4 of 6	ENSP00000514391.1
	CFHR1	ENST00000699455.1		c.280G>T	p.Glu94*	stop_gained	Exon 3 of 5	ENSP00000514392.1

Frequencies

GnomAD3 genomes Cov.: 12

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1016242 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 508124

African (AFR) AF: 0.00 AC: 0 AN: 15690

American (AMR) AF: 0.00 AC: 0 AN: 34284

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 17380

East Asian (EAS) AF: 0.00 AC: 0 AN: 31876

South Asian (SAS) AF: 0.00 AC: 0 AN: 58660

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 43098

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3662

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 769486

Other (OTH) AF: 0.00 AC: 0 AN: 42106

GnomAD4 genome Cov.: 12

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Benign	-0.031	T
BayesDel_noAF	Benign	-0.28
CADD	Pathogenic	26
DANN	Benign	0.85
Eigen	Benign	-0.30
Eigen_PC	Benign	-0.69
FATHMM_MKL	Benign	0.099	N
PhyloP100		-0.075
Vest4		0.70
GERP RS		-3.7
Mutation Taster		=86/114	disease causing (fs/PTC)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs388862; hg19: chr1-196797292;