chr1-196825316-G-A

Position:

• chr1-196825316-G-A

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.59-161G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.015 (380 hom., cov: 18)
  • Exomes 𝑓: 0.0013 (111 hom.)
• Consequence: CFHR1 NM_002113.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.0420

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BP6: Variant 1-196825316-G-A is Benign according to our data. Variant chr1-196825316-G-A is described in ClinVar as [Benign]. Clinvar id is 1238527.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.083 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CFHR1	NM_002113.3	c.59-161G>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.59-161G>A		intron_variant		1	NM_002113.3	ENSP00000314299.5

Frequencies

GnomAD3 genomes AF: 0.0153 AC: 1357 AN: 88798 Hom.: 378 Cov.: 18

Gnomad AFR AF: 0.0869

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00707

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00526

Gnomad NFE AF: 0.000189

Gnomad OTH AF: 0.00850

GnomAD4 exome AF: 0.00125 AC: 497 AN: 396622 Hom.: 111 Cov.: 4 AF XY: 0.00111 AC XY: 232 AN XY: 209472

Gnomad4 AFR exome AF: 0.0437

Gnomad4 AMR exome AF: 0.00187

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000193

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000166

Gnomad4 OTH exome AF: 0.00262

GnomAD4 genome AF: 0.0153 AC: 1363 AN: 88846 Hom.: 380 Cov.: 18 AF XY: 0.0156 AC XY: 675 AN XY: 43172

Gnomad4 AFR AF: 0.0870

Gnomad4 AMR AF: 0.00707

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000189

Gnomad4 OTH AF: 0.00842

Alfa AF: 0.00851 Hom.: 31

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

Oct 26, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	3.3
DANN	Benign	0.17

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: rs111886512; hg19: chr1-196794446;