chr1-196977292-G-GA

Variant names:

• chr1-196977292-G-GA
• rs138249543
• ENST00000699466.1:c.-198+2178_-198+2179insA

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BS1 BS2

The ENST00000699466.1(CFHR5):​c.-198+2178_-198+2179insA variant causes a intron change involving the alteration of a non-conserved nucleotide. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.014 (30 hom., cov: 0)
• Consequence: CFHR5 ENST00000699466.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.772
• Publications: 0 publications found

Genes affected

CFHR5 (HGNC:24668): (complement factor H related 5) This gene is a member of a small complement factor H (CFH) gene cluster on chromosome 1. Each member of this gene family contains multiple short consensus repeats (SCRs) typical of regulators of complement activation. The protein encoded by this gene has nine SCRs with the first two repeats having heparin binding properties, a region within repeats 5-7 having heparin binding and C reactive protein binding properties, and the C-terminal repeats being similar to a complement component 3 b (C3b) binding domain. This protein co-localizes with C3, binds C3b in a dose-dependent manner, and is recruited to tissues damaged by C-reactive protein. Allelic variations in this gene have been associated, but not causally linked, with two different forms of kidney disease: membranoproliferative glomerulonephritis type II (MPGNII) and hemolytic uraemic syndrome (HUS). [provided by RefSeq, Jan 2010]

CFHR5 Gene-Disease associations (from GenCC):

• C3 glomerulonephritis

  Inheritance: AD Classification: STRONG, MODERATE Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -8 ACMG points.

• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.0135 (1904/141018) while in subpopulation AFR AF = 0.0385 (1510/39246). AF 95% confidence interval is 0.0369. There are 30 homozygotes in GnomAd4. There are 888 alleles in the male GnomAd4 subpopulation. Median coverage is 0. This position passed quality control check.
• BS2: High AC in GnomAd4 at 1904 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000699466.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
There are no transcript annotations for this variant.

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CFHR5	ENST00000699466.1		c.-198+2178_-198+2179insA		intron	N/A	ENSP00000514393.1	A0A8V8TNA3
	CFHR5	ENST00000699467.1		n.127+1704_127+1705insA		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.0135 AC: 1902 AN: 141002 Hom.: 30 Cov.: 0

Gnomad AFR AF: 0.0385

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00529

Gnomad ASJ AF: 0.0178

Gnomad EAS AF: 0.000404

Gnomad SAS AF: 0.000905

Gnomad FIN AF: 0.00428

Gnomad MID AF: 0.00347

Gnomad NFE AF: 0.00316

Gnomad OTH AF: 0.00887

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

GnomAD4 genome AF: 0.0135 AC: 1904 AN: 141018 Hom.: 30 Cov.: 0 AF XY: 0.0130 AC XY: 888 AN XY: 68224

African (AFR) AF: 0.0385 AC: 1510 AN: 39246

American (AMR) AF: 0.00528 AC: 75 AN: 14196

Ashkenazi Jewish (ASJ) AF: 0.0178 AC: 59 AN: 3310

East Asian (EAS) AF: 0.000406 AC: 2 AN: 4930

South Asian (SAS) AF: 0.000911 AC: 4 AN: 4390

European-Finnish (FIN) AF: 0.00428 AC: 34 AN: 7948

Middle Eastern (MID) AF: 0.00373 AC: 1 AN: 268

European-Non Finnish (NFE) AF: 0.00316 AC: 202 AN: 63952

Other (OTH) AF: 0.00882 AC: 17 AN: 1928

Alfa AF: 0.000514 Hom.: 123

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		-0.77

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs138249543; hg19: chr1-196946422;