rs1750311

Positions:

• chr1-196985095-C-A
• chr1-196985095-C-T

Variant summary

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

The NM_030787.4(CFHR5):​c.430+958C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.418 in 151,882 control chromosomes in the GnomAD database, including 15,509 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 0.42 (15509 hom., cov: 32)
• Consequence: CFHR5 NM_030787.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.59

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.98).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.681 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CFHR5	NM_030787.4	c.430+958C>A		intron_variant		ENST00000256785.5	NP_110414.1
CFHR5	XM_011510020.3	c.439+958C>A		intron_variant			XP_011508322.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CFHR5	ENST00000256785.5	c.430+958C>A		intron_variant		1	NM_030787.4	ENSP00000256785.4
CFHR5	ENST00000699466.1	c.175+958C>A		intron_variant				ENSP00000514393.1
CFHR5	ENST00000699468.1	c.-25+7415C>A		intron_variant				ENSP00000514394.1
CFHR5	ENST00000699467.1	n.499+958C>A		intron_variant

Frequencies

GnomAD3 genomes AF: 0.418 AC: 63444 AN: 151764 Hom.: 15475 Cov.: 32

Gnomad AFR AF: 0.687

Gnomad AMI AF: 0.181

Gnomad AMR AF: 0.313

Gnomad ASJ AF: 0.406

Gnomad EAS AF: 0.180

Gnomad SAS AF: 0.302

Gnomad FIN AF: 0.295

Gnomad MID AF: 0.459

Gnomad NFE AF: 0.327

Gnomad OTH AF: 0.408

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

GnomAD4 genome AF: 0.418 AC: 63519 AN: 151882 Hom.: 15509 Cov.: 32 AF XY: 0.413 AC XY: 30611 AN XY: 74198

Gnomad4 AFR AF: 0.688

Gnomad4 AMR AF: 0.312

Gnomad4 ASJ AF: 0.406

Gnomad4 EAS AF: 0.181

Gnomad4 SAS AF: 0.301

Gnomad4 FIN AF: 0.295

Gnomad4 NFE AF: 0.327

Gnomad4 OTH AF: 0.406

Alfa AF: 0.330 Hom.: 14437

Bravo AF: 0.429

Asia WGS AF: 0.252 AC: 876 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	0.71
DANN	Benign	0.68

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs1750311; hg19: chr1-196954225;