1-196825737-G-A

Position:

• chr1-196825737-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.253+66G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.145 in 1,386,212 control chromosomes in the GnomAD database, including 40,534 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.16 (5403 hom., cov: 24)
  • Exomes 𝑓: 0.14 (35131 hom.)
• Consequence: CFHR1 NM_002113.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.30

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BP6: Variant 1-196825737-G-A is Benign according to our data. Variant chr1-196825737-G-A is described in ClinVar as [Benign]. Clinvar id is 1283579.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.229 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CFHR1	NM_002113.3	c.253+66G>A		intron_variant		ENST00000320493.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CFHR1	ENST00000320493.10	c.253+66G>A		intron_variant		1	NM_002113.3	P1

Frequencies

GnomAD3 genomes AF: 0.160 AC: 21459 AN: 133986 Hom.: 5399 Cov.: 24

Gnomad AFR AF: 0.234

Gnomad AMI AF: 0.0295

Gnomad AMR AF: 0.151

Gnomad ASJ AF: 0.166

Gnomad EAS AF: 0.111

Gnomad SAS AF: 0.0714

Gnomad FIN AF: 0.0696

Gnomad MID AF: 0.273

Gnomad NFE AF: 0.151

Gnomad OTH AF: 0.166

GnomAD4 exome AF: 0.143 AC: 179523 AN: 1252110 Hom.: 35131 Cov.: 22 AF XY: 0.142 AC XY: 88774 AN XY: 626204

Gnomad4 AFR exome AF: 0.242

Gnomad4 AMR exome AF: 0.116

Gnomad4 ASJ exome AF: 0.174

Gnomad4 EAS exome AF: 0.109

Gnomad4 SAS exome AF: 0.0803

Gnomad4 FIN exome AF: 0.0777

Gnomad4 NFE exome AF: 0.151

Gnomad4 OTH exome AF: 0.150

GnomAD4 genome AF: 0.160 AC: 21466 AN: 134102 Hom.: 5403 Cov.: 24 AF XY: 0.155 AC XY: 10106 AN XY: 65142

Gnomad4 AFR AF: 0.234

Gnomad4 AMR AF: 0.151

Gnomad4 ASJ AF: 0.166

Gnomad4 EAS AF: 0.111

Gnomad4 SAS AF: 0.0714

Gnomad4 FIN AF: 0.0696

Gnomad4 NFE AF: 0.151

Gnomad4 OTH AF: 0.164

Alfa AF: 0.149 Hom.: 593

Asia WGS AF: 0.0820 AC: 268 AN: 3244

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	-0.90
CADD	Benign	1.6
DANN	Benign	0.39

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs372075; hg19: chr1-196794867;