1-196977292-GA-G

Position:

• chr1-196977292-GA-G

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The ENST00000699466.1(CFHR5):​c.-198+2192del variant causes a intron change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.37 (10228 hom., cov: 0)
• Consequence: CFHR5 ENST00000699466.1 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• 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 -10 ACMG points.

• BP6: Variant 1-196977292-GA-G is Benign according to our data. Variant chr1-196977292-GA-G is described in ClinVar as [Benign]. Clinvar id is 1240837.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.679 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CFHR5	XM_011510020.3	c.67+2192del		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CFHR5	ENST00000699466.1	c.-198+2192del		intron_variant
CFHR5	ENST00000699467.1	n.127+1718del		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.369 AC: 52085 AN: 140970 Hom.: 10224 Cov.: 0

Gnomad AFR AF: 0.487

Gnomad AMI AF: 0.118

Gnomad AMR AF: 0.460

Gnomad ASJ AF: 0.282

Gnomad EAS AF: 0.698

Gnomad SAS AF: 0.443

Gnomad FIN AF: 0.345

Gnomad MID AF: 0.243

Gnomad NFE AF: 0.259

Gnomad OTH AF: 0.376

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

GnomAD4 genome AF: 0.369 AC: 52092 AN: 140988 Hom.: 10228 Cov.: 0 AF XY: 0.380 AC XY: 25947 AN XY: 68214

Gnomad4 AFR AF: 0.486

Gnomad4 AMR AF: 0.460

Gnomad4 ASJ AF: 0.282

Gnomad4 EAS AF: 0.698

Gnomad4 SAS AF: 0.443

Gnomad4 FIN AF: 0.345

Gnomad4 NFE AF: 0.259

Gnomad4 OTH AF: 0.375

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 18, 2021

- -

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;