rs6694672

Positions:

• chr1-196976659-T-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000699466.1(CFHR5):​c.-198+1545T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.182 in 151,970 control chromosomes in the GnomAD database, including 4,367 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.18 (4367 hom., cov: 32)
• Consequence: CFHR5 ENST00000699466.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0620

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.428 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CFHR5	XM_011510020.3	c.67+1545T>G		intron_variant			XP_011508322.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CFHR5	ENST00000699466.1	c.-198+1545T>G		intron_variant				ENSP00000514393
CFHR5	ENST00000699467.1	n.127+1071T>G		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.182 AC: 27667 AN: 151852 Hom.: 4361 Cov.: 32

Gnomad AFR AF: 0.433

Gnomad AMI AF: 0.0450

Gnomad AMR AF: 0.114

Gnomad ASJ AF: 0.0877

Gnomad EAS AF: 0.000772

Gnomad SAS AF: 0.101

Gnomad FIN AF: 0.0711

Gnomad MID AF: 0.114

Gnomad NFE AF: 0.0895

Gnomad OTH AF: 0.166

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

GnomAD4 genome AF: 0.182 AC: 27692 AN: 151970 Hom.: 4367 Cov.: 32 AF XY: 0.179 AC XY: 13330 AN XY: 74276

Gnomad4 AFR AF: 0.433

Gnomad4 AMR AF: 0.114

Gnomad4 ASJ AF: 0.0877

Gnomad4 EAS AF: 0.000773

Gnomad4 SAS AF: 0.100

Gnomad4 FIN AF: 0.0711

Gnomad4 NFE AF: 0.0895

Gnomad4 OTH AF: 0.164

Alfa AF: 0.148 Hom.: 487

Bravo AF: 0.196

Asia WGS AF: 0.0710 AC: 246 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	2.5
DANN	Benign	0.66

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs6694672; hg19: chr1-196945789;