Variant 1-196949611-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_005666.4(CFHR2):c.215G>A(p.Cys72Tyr) variant causes a missense change. The variant allele was found at a frequency of 0.0251 in 1,613,888 control chromosomes in the GnomAD database, including 800 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.021 ( 69 hom., cov: 33)

Exomes 𝑓: 0.026 ( 731 hom. )

Consequence

CFHR2
NM_005666.4 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 3.64

Variant links:

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]

CFHR2 links:

CFHR2 (HGNC:):

CFHR2 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.002033323).

BP6

Variant 1-196949611-G-A is Benign according to our data. Variant chr1-196949611-G-A is described in ClinVar as [Benign]. Clinvar id is 1712442.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr1-196949611-G-A is described in Lovd as [Likely_benign].

BA1

GnomAdExome4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.0931 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CFHR2	NM_005666.4 linkuse as main transcript	c.215G>A	p.Cys72Tyr	missense_variant	2/5	ENST00000367415.8	NP_005657.1	P36980-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CFHR2	ENST00000367415.8 linkuse as main transcript	c.215G>A	p.Cys72Tyr	missense_variant	2/5	1	NM_005666.4	ENSP00000356385.4		P36980-1

Frequencies

GnomAD3 genomes

AF:

0.0208

AC:

3162

AN:

152204

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00494

Gnomad AMI

AF:

0.163

Gnomad AMR

AF:

0.0386

Gnomad ASJ

AF:

0.0115

Gnomad EAS

AF:

0.000577

Gnomad SAS

AF:

0.0325

Gnomad FIN

AF:

0.0295

Gnomad MID

AF:

0.00949

Gnomad NFE

AF:

0.0246

Gnomad OTH

AF:

0.0129

GnomAD3 exomes

AF:

0.0326

AC:

8182

AN:

251196

Hom.:

301

AF XY:

0.0298

AC XY:

4045

AN XY:

135754

show subpopulations

Gnomad AFR exome

AF:

0.00400

Gnomad AMR exome

AF:

0.105

Gnomad ASJ exome

AF:

0.0120

Gnomad EAS exome

AF:

0.000217

Gnomad SAS exome

AF:

0.0298

Gnomad FIN exome

AF:

0.0301

Gnomad NFE exome

AF:

0.0229

Gnomad OTH exome

AF:

0.0299

GnomAD4 exome

AF:

0.0256

AC:

37386

AN:

1461566

Hom.:

731

Cov.:

AF XY:

0.0252

AC XY:

18294

AN XY:

727092

show subpopulations

Gnomad4 AFR exome

AF:

0.00394

Gnomad4 AMR exome

AF:

0.0955

Gnomad4 ASJ exome

AF:

0.0124

Gnomad4 EAS exome

AF:

0.0000504

Gnomad4 SAS exome

AF:

0.0305

Gnomad4 FIN exome

AF:

0.0281

Gnomad4 NFE exome

AF:

0.0245

Gnomad4 OTH exome

AF:

0.0207

GnomAD4 genome

AF:

0.0208

AC:

3163

AN:

152322

Hom.:

Cov.:

AF XY:

0.0210

AC XY:

1564

AN XY:

74494

show subpopulations

Gnomad4 AFR

AF:

0.00493

Gnomad4 AMR

AF:

0.0386

Gnomad4 ASJ

AF:

0.0115

Gnomad4 EAS

AF:

0.000578

Gnomad4 SAS

AF:

0.0327

Gnomad4 FIN

AF:

0.0295

Gnomad4 NFE

AF:

0.0246

Gnomad4 OTH

AF:

0.0128

Alfa

AF:

0.0201

Hom.:

Bravo

AF:

0.0220

TwinsUK

AF:

0.0216

AC:

ALSPAC

AF:

0.0254

AC:

ESP6500AA

AF:

0.00681

AC:

ESP6500EA

AF:

0.0256

AC:

220

ExAC

AF:

0.0295

AC:

3586

Asia WGS

AF:

0.00924

AC:

AN:

3478

EpiCase

AF:

0.0209

EpiControl

AF:

0.0206

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Atypical hemolytic-uremic syndrome

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome Diagnostics Laboratory, The Hospital for Sick Children

Jul 08, 2022

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.93

BayesDel_addAF

Benign

-0.24

BayesDel_noAF

Uncertain

-0.030

CADD

Benign

DANN

Benign

0.94

DEOGEN2

Benign

0.30

.;T;T

Eigen

Benign

0.18

Eigen_PC

Benign

-0.066

FATHMM_MKL

Benign

0.35

LIST_S2

Benign

0.78

T;T;T

MetaRNN

Benign

0.0020

T;T;T

MetaSVM

Uncertain

0.20

MutationAssessor

Pathogenic

3.1

.;M;.

PrimateAI

Benign

0.46

PROVEAN

Pathogenic

-10

.;D;.

REVEL

Uncertain

0.42

Sift

Pathogenic

0.0

.;D;.

Sift4G

Pathogenic

0.0

.;D;D

Polyphen

1.0

.;D;.

Vest4

0.60, 0.58

MPC

0.025

ClinPred

0.14

GERP RS

3.3

Varity_R

0.89

gMVP

0.83

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over