rs1759016

chr1-196983368-C-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_030787.4(CFHR5):c.253+289C>T 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 152,040 control chromosomes in the GnomAD database, including 15,529 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.42 (15529 hom., cov: 33)
• Consequence: CFHR5 NM_030787.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.225

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.02).
• BP6: Variant 1-196983368-C-T is Benign according to our data. Variant chr1-196983368-C-T is described in ClinVar as [Benign]. Clinvar id is 1278644.Status of the report is criteria_provided_single_submitter, 1 stars.
• 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	UniProt
CFHR5	NM_030787.4	c.253+289C>T		intron_variant		ENST00000256785.5
CFHR5	XM_011510020.3	c.262+289C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CFHR5	ENST00000256785.5	c.253+289C>T		intron_variant		1	NM_030787.4	P1
CFHR5	ENST00000699466.1	c.-3+289C>T		intron_variant
CFHR5	ENST00000699468.1	c.-25+5688C>T		intron_variant
CFHR5	ENST00000699467.1	n.322+289C>T		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.418 AC: 63501 AN: 151922 Hom.: 15495 Cov.: 33

Gnomad AFR AF: 0.688

Gnomad AMI AF: 0.181

Gnomad AMR AF: 0.313

Gnomad ASJ AF: 0.407

Gnomad EAS AF: 0.180

Gnomad SAS AF: 0.302

Gnomad FIN AF: 0.294

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: 63576 AN: 152040 Hom.: 15529 Cov.: 33 AF XY: 0.412 AC XY: 30656 AN XY: 74326

Gnomad4 AFR AF: 0.688

Gnomad4 AMR AF: 0.313

Gnomad4 ASJ AF: 0.407

Gnomad4 EAS AF: 0.180

Gnomad4 SAS AF: 0.301

Gnomad4 FIN AF: 0.294

Gnomad4 NFE AF: 0.327

Gnomad4 OTH AF: 0.406

Alfa AF: 0.317 Hom.: 5589

Bravo AF: 0.429

Asia WGS AF: 0.252 AC: 876 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Nov 10, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
Cadd	Benign	4.2
Dann	Benign	0.46

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: rs1759016; hg19: chr1-196952498;