chr1-196977292-GA-G

Variant names:

• chr1-196977292-GA-G
• rs138249543
• ENST00000699466.1:c.-198+2179delA

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The ENST00000699466.1(CFHR5):​c.-198+2179delA 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
• 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 -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 VariationId 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.

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+2179delA		intron	N/A	ENSP00000514393.1	A0A8V8TNA3
	CFHR5	ENST00000699467.1		n.127+1705delA		intron	N/A

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

African (AFR) AF: 0.486 AC: 19062 AN: 39202

American (AMR) AF: 0.460 AC: 6531 AN: 14188

Ashkenazi Jewish (ASJ) AF: 0.282 AC: 937 AN: 3320

East Asian (EAS) AF: 0.698 AC: 3442 AN: 4930

South Asian (SAS) AF: 0.443 AC: 1941 AN: 4386

European-Finnish (FIN) AF: 0.345 AC: 2742 AN: 7940

Middle Eastern (MID) AF: 0.235 AC: 63 AN: 268

European-Non Finnish (NFE) AF: 0.259 AC: 16550 AN: 63974

Other (OTH) AF: 0.375 AC: 724 AN: 1930

Alfa AF: 0.0964 Hom.: 123

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

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; COSMIC: COSV56820636;