1-196977292-GAAA-GA

Variant names:

• chr1-196977292-GAA-G
• rs138249543
• ENST00000699466.1:c.-198+2179_-198+2180delAA

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS2

The ENST00000699466.1(CFHR5):​c.-198+2179_-198+2180delAA 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 0.00035 (0 hom., cov: 0)
• Consequence: CFHR5 ENST00000699466.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0140

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]

ACMG classification

Verdict is Likely_benign. Variant got -4 ACMG points.

• BS2: High AC in GnomAd4 at 50 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CFHR5	XM_011510020.3	c.67+2191_67+2192delAA		intron_variant	Intron 1 of 9		XP_011508322.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CFHR5	ENST00000699466.1	c.-198+2179_-198+2180delAA		intron_variant	Intron 1 of 9			ENSP00000514393.1
CFHR5	ENST00000699467.1	n.127+1705_127+1706delAA		intron_variant	Intron 1 of 9

Frequencies

GnomAD3 genomes AF: 0.000354 AC: 50 AN: 141086 Hom.: 0 Cov.: 0

Gnomad AFR AF: 0.000689

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000282

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000808

Gnomad SAS AF: 0.000226

Gnomad FIN AF: 0.000503

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000156

Gnomad OTH AF: 0.00

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

GnomAD4 genome AF: 0.000354 AC: 50 AN: 141102 Hom.: 0 Cov.: 0 AF XY: 0.000395 AC XY: 27 AN XY: 68280

Gnomad4 AFR AF: 0.000713

Gnomad4 AMR AF: 0.000211

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.000811

Gnomad4 SAS AF: 0.000228

Gnomad4 FIN AF: 0.000503

Gnomad4 NFE AF: 0.000156

Gnomad4 OTH AF: 0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs138249543; hg19: chr1-196946422;