rs12116643

Positions:

• chr1-197004053-T-C
• chr1-197004053-T-G

Variant summary

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

The NM_030787.4(CFHR5):​c.1331-608T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.197 in 152,094 control chromosomes in the GnomAD database, including 4,158 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 0.20 (4158 hom., cov: 32)
• Consequence: CFHR5 NM_030787.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.215

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=-0.95).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.671 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CFHR5	NM_030787.4	c.1331-608T>C		intron_variant		ENST00000256785.5
CFHR5	XM_011510020.3	c.1340-608T>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CFHR5	ENST00000256785.5	c.1331-608T>C		intron_variant		1	NM_030787.4	P1

Frequencies

GnomAD3 genomes AF: 0.197 AC: 29925 AN: 151976 Hom.: 4148 Cov.: 32

Gnomad AFR AF: 0.115

Gnomad AMI AF: 0.0647

Gnomad AMR AF: 0.343

Gnomad ASJ AF: 0.188

Gnomad EAS AF: 0.690

Gnomad SAS AF: 0.323

Gnomad FIN AF: 0.249

Gnomad MID AF: 0.123

Gnomad NFE AF: 0.162

Gnomad OTH AF: 0.203

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

GnomAD4 genome AF: 0.197 AC: 29946 AN: 152094 Hom.: 4158 Cov.: 32 AF XY: 0.208 AC XY: 15493 AN XY: 74334

Gnomad4 AFR AF: 0.115

Gnomad4 AMR AF: 0.344

Gnomad4 ASJ AF: 0.188

Gnomad4 EAS AF: 0.690

Gnomad4 SAS AF: 0.322

Gnomad4 FIN AF: 0.249

Gnomad4 NFE AF: 0.162

Gnomad4 OTH AF: 0.204

Alfa AF: 0.160 Hom.: 2202

Bravo AF: 0.203

Asia WGS AF: 0.495 AC: 1716 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	4.4
DANN	Benign	0.56

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs12116643; hg19: chr1-196973183;