1-196820070-A-G

Position:

• chr1-196820070-A-G

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.58+168A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.225 in 143,378 control chromosomes in the GnomAD database, including 3,868 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.22 (3868 hom., cov: 22)
• Consequence: CFHR1 NM_002113.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.979

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=-0.86).
• BP6: Variant 1-196820070-A-G is Benign according to our data. Variant chr1-196820070-A-G is described in ClinVar as [Benign]. Clinvar id is 1245326.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.381 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CFHR1	NM_002113.3	c.58+168A>G		intron_variant		ENST00000320493.10	NP_002104.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CFHR1	ENST00000320493.10	c.58+168A>G		intron_variant		1	NM_002113.3	ENSP00000314299.5

Frequencies

GnomAD3 genomes AF: 0.225 AC: 32194 AN: 143272 Hom.: 3857 Cov.: 22

Gnomad AFR AF: 0.179

Gnomad AMI AF: 0.138

Gnomad AMR AF: 0.315

Gnomad ASJ AF: 0.277

Gnomad EAS AF: 0.395

Gnomad SAS AF: 0.250

Gnomad FIN AF: 0.251

Gnomad MID AF: 0.0966

Gnomad NFE AF: 0.212

Gnomad OTH AF: 0.229

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.225 AC: 32233 AN: 143378 Hom.: 3868 Cov.: 22 AF XY: 0.229 AC XY: 15947 AN XY: 69686

Gnomad4 AFR AF: 0.179

Gnomad4 AMR AF: 0.316

Gnomad4 ASJ AF: 0.277

Gnomad4 EAS AF: 0.396

Gnomad4 SAS AF: 0.250

Gnomad4 FIN AF: 0.251

Gnomad4 NFE AF: 0.212

Gnomad4 OTH AF: 0.231

Alfa AF: 0.215 Hom.: 393

Bravo AF: 0.232

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	-0.86
CADD	Benign	9.2
DANN	Benign	0.89

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: rs424772; hg19: chr1-196789200; COSMIC: COSV57628523;