1-196984021-T-G

Position:

• chr1-196984021-T-G

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_030787.4(CFHR5):​c.314T>G​(p.Leu105Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (no stars).

• Frequency: Genomes: not found (cov: 32)
• Consequence: CFHR5 NM_030787.4 missense
• Clinical Significance: Uncertain significance no assertion criteria provided U:1 O:1
• Conservation: PhyloP100: -0.110

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 Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CFHR5	NM_030787.4	c.314T>G	p.Leu105Arg	missense_variant	3/10	ENST00000256785.5	NP_110414.1
CFHR5	XM_011510020.3	c.323T>G	p.Leu108Arg	missense_variant	3/10		XP_011508322.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CFHR5	ENST00000256785.5	c.314T>G	p.Leu105Arg	missense_variant	3/10	1	NM_030787.4	ENSP00000256785	P1
CFHR5	ENST00000699466.1	c.59T>G	p.Leu20Arg	missense_variant	3/10			ENSP00000514393
CFHR5	ENST00000699468.1	c.-25+6341T>G		intron_variant				ENSP00000514394
CFHR5	ENST00000699467.1	n.383T>G		non_coding_transcript_exon_variant	3/10

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 29

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1 Other:1

Revision: no assertion criteria provided

Submissions by phenotype

Variant of unknown significance Uncertain:1

Uncertain significance, no assertion criteria provided

literature only

OMIM

Jul 01, 2012

- -

not provided Other:1

not provided, no classification provided

literature only

UniProtKB/Swiss-Prot

-

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.10
BayesDel_addAF	Uncertain	0.040	T
BayesDel_noAF	Benign	-0.18
CADD	Benign	9.2
DANN	Benign	0.78
DEOGEN2	Benign	0.041	T
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.3
FATHMM_MKL	Benign	0.011	N
LIST_S2	Benign	0.58	T
M_CAP	Benign	0.025	D
MetaRNN	Uncertain	0.49	T
MetaSVM	Benign	-0.94	T
MutationAssessor	Uncertain	2.1	M
MutationTaster	Benign	1.0	N;N
PrimateAI	Benign	0.26	T
PROVEAN	Uncertain	-2.8	D
REVEL	Uncertain	0.32
Sift	Benign	0.81	T
Sift4G	Benign	0.27	T
Polyphen		0.63	P
Vest4		0.81
MutPred		0.40		Gain of disorder (P = 0.0364);
MVP		0.40
MPC		0.11
ClinPred		0.33	T
GERP RS		-7.5
Varity_R		0.26
gMVP		0.50

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs318240754; hg19: chr1-196953151;