1-196977292-GAAA-GAAAAA

Variant names:

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

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BS2

The ENST00000699466.1(CFHR5):​c.-198+2178_-198+2179insAA 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 0.0029 (1 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: Likely_benign. The variant received -4 ACMG points.

• BS2: High AC in GnomAd4 at 415 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+2179insAA		intron	N/A	ENSP00000514393.1	A0A8V8TNA3
	CFHR5	ENST00000699467.1		n.127+1704_127+1705insAA		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.00292 AC: 412 AN: 141084 Hom.: 1 Cov.: 0

Gnomad AFR AF: 0.00937

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000846

Gnomad ASJ AF: 0.00663

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000226

Gnomad FIN AF: 0.000252

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000469

Gnomad OTH AF: 0.00261

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

GnomAD4 genome AF: 0.00294 AC: 415 AN: 141102 Hom.: 1 Cov.: 0 AF XY: 0.00277 AC XY: 189 AN XY: 68274

African (AFR) AF: 0.00943 AC: 370 AN: 39252

American (AMR) AF: 0.000845 AC: 12 AN: 14202

Ashkenazi Jewish (ASJ) AF: 0.00663 AC: 22 AN: 3320

East Asian (EAS) AF: 0.00 AC: 0 AN: 4932

South Asian (SAS) AF: 0.000228 AC: 1 AN: 4390

European-Finnish (FIN) AF: 0.000252 AC: 2 AN: 7952

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 268

European-Non Finnish (NFE) AF: 0.0000469 AC: 3 AN: 64008

Other (OTH) AF: 0.00259 AC: 5 AN: 1928

Alfa AF: 0.00 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;