Variant 1-196949608-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2

The NM_005666.4(CFHR2):c.212C>T(p.Thr71Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00477 in 1,613,916 control chromosomes in the GnomAD database, including 39 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★). Synonymous variant affecting the same amino acid position (i.e. T71T) has been classified as Benign.

Frequency

Genomes: 𝑓 0.0037 ( 3 hom., cov: 33)

Exomes 𝑓: 0.0049 ( 36 hom. )

Consequence

CFHR2
NM_005666.4 missense

Scores

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -2.18

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -16 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.028270662).

BP6

Variant 1-196949608-C-T is Benign according to our data. Variant chr1-196949608-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 1712465.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr1-196949608-C-T is described in Lovd as [Likely_benign].

BS2

High Homozygotes in GnomAd4 at 3 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CFHR2	NM_005666.4 linkuse as main transcript	c.212C>T	p.Thr71Met	missense_variant	2/5	ENST00000367415.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CFHR2	ENST00000367415.8 linkuse as main transcript	c.212C>T	p.Thr71Met	missense_variant	2/5	1	NM_005666.4	P2	P36980-1

Frequencies

GnomAD3 genomes

AF:

0.00373

AC:

567

AN:

152162

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000676

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000916

Gnomad ASJ

AF:

0.000288

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00290

Gnomad FIN

AF:

0.00396

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00681

Gnomad OTH

AF:

0.00239

GnomAD3 exomes

AF:

0.00365

AC:

916

AN:

251228

Hom.:

AF XY:

0.00389

AC XY:

528

AN XY:

135772

show subpopulations

Gnomad AFR exome

AF:

0.000554

Gnomad AMR exome

AF:

0.00113

Gnomad ASJ exome

AF:

0.0000992

Gnomad EAS exome

AF:

0.0000544

Gnomad SAS exome

AF:

0.00314

Gnomad FIN exome

AF:

0.00531

Gnomad NFE exome

AF:

0.00560

Gnomad OTH exome

AF:

0.00310

GnomAD4 exome

AF:

0.00487

AC:

7124

AN:

1461636

Hom.:

Cov.:

AF XY:

0.00493

AC XY:

3584

AN XY:

727118

show subpopulations

Gnomad4 AFR exome

AF:

0.000807

Gnomad4 AMR exome

AF:

0.00128

Gnomad4 ASJ exome

AF:

0.000115

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.00443

Gnomad4 FIN exome

AF:

0.00653

Gnomad4 NFE exome

AF:

0.00545

Gnomad4 OTH exome

AF:

0.00386

GnomAD4 genome

AF:

0.00373

AC:

568

AN:

152280

Hom.:

Cov.:

AF XY:

0.00363

AC XY:

270

AN XY:

74474

show subpopulations

Gnomad4 AFR

AF:

0.000674

Gnomad4 AMR

AF:

0.000915

Gnomad4 ASJ

AF:

0.000288

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00311

Gnomad4 FIN

AF:

0.00396

Gnomad4 NFE

AF:

0.00681

Gnomad4 OTH

AF:

0.00237

Alfa

AF:

0.00544

Hom.:

Bravo

AF:

0.00312

TwinsUK

AF:

0.00405

AC:

ALSPAC

AF:

0.00441

AC:

ESP6500AA

AF:

0.000227

AC:

ESP6500EA

AF:

0.00628

AC:

ExAC

AF:

0.00396

AC:

481

EpiCase

AF:

0.00507

EpiControl

AF:

0.00450

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Jul 01, 2024

CFHR2: BP4, BS2 -

Atypical hemolytic-uremic syndrome

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Genome Diagnostics Laboratory, The Hospital for Sick Children

Oct 01, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.51

BayesDel_noAF

Benign

-0.50

CADD

Benign

0.038

DANN

Benign

0.81

DEOGEN2

Benign

0.015

.;T;T

Eigen

Benign

-0.98

Eigen_PC

Benign

-1.1

FATHMM_MKL

Benign

0.0077

LIST_S2

Benign

0.63

T;T;T

M_CAP

Benign

0.030

MetaRNN

Benign

0.028

T;T;T

MetaSVM

Benign

-0.99

MutationAssessor

Benign

1.4

.;L;.

MutationTaster

Benign

1.0

N;N

PrimateAI

Benign

0.29

PROVEAN

Uncertain

-2.5

.;D;.

REVEL

Benign

0.11

Sift

Benign

0.039

.;D;.

Sift4G

Benign

0.27

.;T;T

Polyphen

0.21

.;B;.

Vest4

0.15, 0.14

MVP

0.39

MPC

0.022

ClinPred

0.019

GERP RS

-1.6

Varity_R

0.030

gMVP

0.26

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.050

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