rs413979

Positions:

• chr1-196832482-G-A
• chr1-196832482-G-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000699456.1(CFHR1):​n.966+599G>A variant causes a intron, non coding transcript 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, non_coding_transcript
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.02

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 -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CFHR1	ENST00000699456.1	n.966+599G>A		intron_variant, non_coding_transcript_variant

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

Gnomad4 AFR AF: 0.667

Gnomad4 AMR AF: 0.554

Gnomad4 ASJ AF: 0.522

Gnomad4 EAS AF: 0.548

Gnomad4 SAS AF: 0.442

Gnomad4 FIN AF: 0.383

Gnomad4 NFE AF: 0.417

Gnomad4 OTH AF: 0.513

Alfa AF: 0.475 Hom.: 2547

Asia WGS AF: 0.518 AC: 1671 AN: 3226

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	1.4
DANN	Benign	0.40

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: rs413979; hg19: chr1-196801612;