ENST00000699466.1:c.-198+2178_-198+2179insA

Variant names:

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

Variant summary

Our verdict is Benign. Variant got -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

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 Benign. Variant got -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 male gnomad4 subpopulation. Median coverage is 0. This position pass quality control queck.
• BS2: High AC in GnomAd4 at 1904 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CFHR5	XM_011510020.3	c.67+2192dupA		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+2178_-198+2179insA		intron_variant	Intron 1 of 9			ENSP00000514393.1
CFHR5	ENST00000699467.1	n.127+1704_127+1705insA		intron_variant	Intron 1 of 9

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

Gnomad4 AFR AF: 0.0385

Gnomad4 AMR AF: 0.00528

Gnomad4 ASJ AF: 0.0178

Gnomad4 EAS AF: 0.000406

Gnomad4 SAS AF: 0.000911

Gnomad4 FIN AF: 0.00428

Gnomad4 NFE AF: 0.00316

Gnomad4 OTH AF: 0.00882

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;