1-196832482-G-A

Variant names:

• chr1-196832482-G-A
• rs413979
• ENST00000699456.1:n.966+599G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000699456.1(CFHR1):​n.966+599G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.495 in 132,990 control chromosomes in the GnomAD database, including 22,746 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.49 (22746 hom., cov: 23)
• Consequence: CFHR1 ENST00000699456.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.02
• Publications: 3 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.02).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.659 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000699456.1. 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

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CFHR1	ENST00000699456.1		n.966+599G>A		intron	N/A
	CFHR1	ENST00000699454.1		c.*483G>A		downstream_gene	N/A	ENSP00000514391.1

Frequencies

GnomAD3 genomes AF: 0.494 AC: 65697 AN: 132876 Hom.: 22706 Cov.: 23

Gnomad AFR AF: 0.667

Gnomad AMI AF: 0.179

Gnomad AMR AF: 0.554

Gnomad ASJ AF: 0.522

Gnomad EAS AF: 0.548

Gnomad SAS AF: 0.441

Gnomad FIN AF: 0.383

Gnomad MID AF: 0.422

Gnomad NFE AF: 0.417

Gnomad OTH AF: 0.512

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

GnomAD4 genome AF: 0.495 AC: 65778 AN: 132990 Hom.: 22746 Cov.: 23 AF XY: 0.496 AC XY: 32009 AN XY: 64564

African (AFR) AF: 0.667 AC: 20503 AN: 30752

American (AMR) AF: 0.554 AC: 7702 AN: 13892

Ashkenazi Jewish (ASJ) AF: 0.522 AC: 1641 AN: 3142

East Asian (EAS) AF: 0.548 AC: 2770 AN: 5052

South Asian (SAS) AF: 0.442 AC: 1717 AN: 3888

European-Finnish (FIN) AF: 0.383 AC: 3720 AN: 9720

Middle Eastern (MID) AF: 0.408 AC: 98 AN: 240

European-Non Finnish (NFE) AF: 0.417 AC: 26542 AN: 63614

Other (OTH) AF: 0.513 AC: 927 AN: 1806

Alfa AF: 0.475 Hom.: 2547

Asia WGS AF: 0.518 AC: 1671 AN: 3226

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	1.4
DANN	Benign	0.40
PhyloP100		-2.0
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs413979; hg19: chr1-196801612;