NM_030787.4:c.58+287C>T

Variant names:

• chr1-196978009-C-T
• rs12731209
• NM_030787.4:c.58+287C>T

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_030787.4(CFHR5):​c.58+287C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.196 in 151,970 control chromosomes in the GnomAD database, including 5,263 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.20 (5263 hom., cov: 32)
• Consequence: CFHR5 NM_030787.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.135
• Publications: 2 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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BP6: Variant 1-196978009-C-T is Benign according to our data. Variant chr1-196978009-C-T is described in ClinVar as [Benign]. Clinvar id is 1277859.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.472 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CFHR5	NM_030787.4	c.58+287C>T		intron_variant	Intron 1 of 9	ENST00000256785.5	NP_110414.1
CFHR5	XM_011510020.3	c.67+2895C>T		intron_variant	Intron 1 of 9		XP_011508322.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CFHR5	ENST00000256785.5	c.58+287C>T		intron_variant	Intron 1 of 9	1	NM_030787.4	ENSP00000256785.4
CFHR5	ENST00000699466.1	c.-198+2895C>T		intron_variant	Intron 1 of 9			ENSP00000514393.1
CFHR5	ENST00000699468.1	c.-25+329C>T		intron_variant	Intron 1 of 5			ENSP00000514394.1
CFHR5	ENST00000699467.1	n.127+2421C>T		intron_variant	Intron 1 of 9

Frequencies

GnomAD3 genomes AF: 0.196 AC: 29715 AN: 151852 Hom.: 5246 Cov.: 32

Gnomad AFR AF: 0.478

Gnomad AMI AF: 0.0451

Gnomad AMR AF: 0.119

Gnomad ASJ AF: 0.102

Gnomad EAS AF: 0.000769

Gnomad SAS AF: 0.101

Gnomad FIN AF: 0.0715

Gnomad MID AF: 0.117

Gnomad NFE AF: 0.0902

Gnomad OTH AF: 0.173

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

GnomAD4 genome AF: 0.196 AC: 29761 AN: 151970 Hom.: 5263 Cov.: 32 AF XY: 0.193 AC XY: 14302 AN XY: 74280

African (AFR) AF: 0.478 AC: 19785 AN: 41402

American (AMR) AF: 0.119 AC: 1817 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.102 AC: 353 AN: 3466

East Asian (EAS) AF: 0.000771 AC: 4 AN: 5188

South Asian (SAS) AF: 0.101 AC: 483 AN: 4800

European-Finnish (FIN) AF: 0.0715 AC: 756 AN: 10576

Middle Eastern (MID) AF: 0.109 AC: 32 AN: 294

European-Non Finnish (NFE) AF: 0.0902 AC: 6128 AN: 67948

Other (OTH) AF: 0.172 AC: 362 AN: 2110

Alfa AF: 0.0639 Hom.: 146

Bravo AF: 0.211

Asia WGS AF: 0.0730 AC: 255 AN: 3476

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Nov 11, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	1.9
DANN	Benign	0.52
PhyloP100		-0.14
PromoterAI		-0.014	Neutral
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs12731209; hg19: chr1-196947139;