chr1-196950869-T-C

Variant names:

• chr1-196950869-T-C
• NM_005666.4:c.271T>C

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_005666.4(CFHR2):​c.271T>C​(p.Phe91Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: CFHR2 NM_005666.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.602
• Publications: 0 publications found

Genes affected

CFHR2 (HGNC:4890): (complement factor H related 2) This gene belongs to a family of complement factor H-related genes (CFHR), which are clustered together with complement factor H gene on chromosome 1, and are involved in regulation of complement. Mutations in CFHR genes have been associated with dense deposit disease and atypical haemolytic-uraemic syndrome. Alternatively spliced transcript variants have been found for this gene. [provided by RefSeq, Aug 2015]

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.22497886).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005666.4. 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
	CFHR2	NM_005666.4	MANE Select	c.271T>C	p.Phe91Leu	missense	Exon 3 of 5	NP_005657.1	P36980-1
	CFHR2	NM_001410924.1		c.76T>C	p.Phe26Leu	missense	Exon 2 of 4	NP_001397853.1	A0A3B3IRW0
	CFHR2	NM_001312672.1		c.58+6931T>C		intron	N/A	NP_001299601.1	A0A3B3IS28

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CFHR2	ENST00000367415.8	TSL:1 MANE Select	c.271T>C	p.Phe91Leu	missense	Exon 3 of 5	ENSP00000356385.4	P36980-1
	CFHR2	ENST00000367421.5	TSL:1	c.526T>C	p.Phe176Leu	missense	Exon 4 of 6	ENSP00000356391.4	A0A3B3IQ51
	CFHR2	ENST00000473386.1	TSL:1	c.58+6931T>C		intron	N/A	ENSP00000497089.1	A0A3B3IS28

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.75
BayesDel_addAF	Benign	-0.14	T
BayesDel_noAF	Benign	-0.45
CADD	Benign	17
DANN	Benign	0.86
DEOGEN2	Benign	0.049	T
Eigen	Benign	-0.51
Eigen_PC	Benign	-0.68
FATHMM_MKL	Benign	0.043	N
LIST_S2	Benign	0.65	T
M_CAP	Benign	0.043	D
MetaRNN	Benign	0.22	T
MetaSVM	Benign	-0.86	T
MutationAssessor	Benign	1.6	L
PhyloP100		0.60
PrimateAI	Benign	0.28	T
PROVEAN	Uncertain	-2.8	D
REVEL	Benign	0.20
Sift	Benign	0.46	T
Sift4G	Benign	0.58	T
Polyphen		0.92	P
Vest4		0.090
MutPred		0.48		Gain of sheet (P = 0.0477)
MVP		0.71
MPC		0.022
ClinPred		0.61	D
GERP RS		2.8
Varity_R		0.10
gMVP		0.28
Mutation Taster		=98/2	polymorphism

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

hg19: chr1-196919999;