NM_005666.4:c.31T>C

Variant names:

• chr1-196943911-T-C
• rs1476183056
• NM_005666.4:c.31T>C

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_005666.4(CFHR2):​c.31T>C​(p.Ser11Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. 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: 𝑓 0.000088 (0 hom., cov: 5)
  • Exomes 𝑓: 0.000096 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: CFHR2 NM_005666.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.837
• 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: Likely_benign. The variant received -2 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.15156403).

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.31T>C	p.Ser11Pro	missense	Exon 1 of 5	NP_005657.1	P36980-1
	CFHR2	NM_001410924.1		c.31T>C	p.Ser11Pro	missense	Exon 1 of 4	NP_001397853.1	A0A3B3IRW0
	CFHR2	NM_001312672.1		c.31T>C	p.Ser11Pro	missense	Exon 1 of 3	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.31T>C	p.Ser11Pro	missense	Exon 1 of 5	ENSP00000356385.4	P36980-1
	CFHR2	ENST00000367421.5	TSL:1	c.31T>C	p.Ser11Pro	missense	Exon 1 of 6	ENSP00000356391.4	A0A3B3IQ51
	CFHR2	ENST00000473386.1	TSL:1	c.31T>C	p.Ser11Pro	missense	Exon 1 of 3	ENSP00000497089.1	A0A3B3IS28

Frequencies

GnomAD3 genomes AF: 0.0000882 AC: 3 AN: 34010 Hom.: 0 Cov.: 5

Gnomad AFR AF: 0.000254

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000963

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000132 AC: 4 AN: 30334 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000333

Gnomad OTH exome AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.0000963 AC: 28 AN: 290856 Hom.: 0 Cov.: 0 AF XY: 0.0000585 AC XY: 9 AN XY: 153826

African (AFR) AF: 0.000194 AC: 1 AN: 5148

American (AMR) AF: 0.00 AC: 0 AN: 13610

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 7680

East Asian (EAS) AF: 0.00 AC: 0 AN: 23382

South Asian (SAS) AF: 0.00 AC: 0 AN: 30408

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 22238

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 998

European-Non Finnish (NFE) AF: 0.000157 AC: 27 AN: 171484

Other (OTH) AF: 0.00 AC: 0 AN: 15908

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.0000882 AC: 3 AN: 34010 Hom.: 0 Cov.: 5 AF XY: 0.0000658 AC XY: 1 AN XY: 15188

African (AFR) AF: 0.000254 AC: 1 AN: 3936

American (AMR) AF: 0.00 AC: 0 AN: 2990

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 1056

East Asian (EAS) AF: 0.00 AC: 0 AN: 2052

South Asian (SAS) AF: 0.00 AC: 0 AN: 862

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 1386

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 94

European-Non Finnish (NFE) AF: 0.0000963 AC: 2 AN: 20764

Other (OTH) AF: 0.00 AC: 0 AN: 424

Alfa AF: 0.0000843 Hom.: 0

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.23	T
BayesDel_noAF	Benign	-0.57
CADD	Benign	4.8
DANN	Benign	0.96
DEOGEN2	Benign	0.0047	T
Eigen	Benign	-0.77
Eigen_PC	Benign	-0.99
FATHMM_MKL	Benign	0.0026	N
LIST_S2	Benign	0.15	T
M_CAP	Benign	0.0044	T
MetaRNN	Benign	0.15	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.0	M
PhyloP100		-0.84
PrimateAI	Benign	0.39	T
PROVEAN	Benign	-0.63	N
REVEL	Benign	0.088
Sift	Benign	0.15	T
Sift4G	Benign	0.12	T
Polyphen		0.94	P
Vest4		0.27
MutPred		0.56		Loss of sheet (P = 0.007)
MVP		0.20
MPC		0.018
ClinPred		0.074	T
GERP RS		-0.26
PromoterAI		0.023	Neutral
Varity_R		0.15
gMVP		0.16
Mutation Taster		=100/0	polymorphism

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: rs1476183056; hg19: chr1-196913041;