rs1750311

Variant names:

• chr1-196985095-C-A
• rs1750311
• NM_030787.4:c.430+958C>A

Your query was ambiguous. Multiple possible variants found:

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

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 7 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 -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_030787.4. 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
	CFHR5	NM_030787.4	MANE Select	c.430+958C>A		intron	N/A	NP_110414.1	Q9BXR6

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CFHR5	ENST00000256785.5	TSL:1 MANE Select	c.430+958C>A		intron	N/A	ENSP00000256785.4	Q9BXR6
	CFHR5	ENST00000875779.1		c.430+958C>A		intron	N/A	ENSP00000545838.1
	CFHR5	ENST00000875778.1		c.430+958C>A		intron	N/A	ENSP00000545837.1

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

African (AFR) AF: 0.688 AC: 28496 AN: 41440

American (AMR) AF: 0.312 AC: 4754 AN: 15236

Ashkenazi Jewish (ASJ) AF: 0.406 AC: 1408 AN: 3468

East Asian (EAS) AF: 0.181 AC: 935 AN: 5172

South Asian (SAS) AF: 0.301 AC: 1444 AN: 4798

European-Finnish (FIN) AF: 0.295 AC: 3102 AN: 10512

Middle Eastern (MID) AF: 0.452 AC: 133 AN: 294

European-Non Finnish (NFE) AF: 0.327 AC: 22226 AN: 67942

Other (OTH) AF: 0.406 AC: 856 AN: 2108

Alfa AF: 0.354 Hom.: 26818

Bravo AF: 0.429

Asia WGS AF: 0.252 AC: 876 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	0.71
DANN	Benign	0.68
PhyloP100		-1.6
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs1750311; hg19: chr1-196954225;