Variant 1-196951018-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_StrongBA1

The NM_005666.4(CFHR2):c.420C>T(p.Cys140=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.252 in 1,613,224 control chromosomes in the GnomAD database, including 60,599 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.23 ( 5503 hom., cov: 32)

Exomes 𝑓: 0.25 ( 55096 hom. )

Consequence

CFHR2
NM_005666.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.747

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.

BP6

Variant 1-196951018-C-T is Benign according to our data. Variant chr1-196951018-C-T is described in ClinVar as [Benign]. Clinvar id is 1231528.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr1-196951018-C-T is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.698 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CFHR2	NM_005666.4 linkuse as main transcript	c.420C>T	p.Cys140=	synonymous_variant	3/5	ENST00000367415.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CFHR2	ENST00000367415.8 linkuse as main transcript	c.420C>T	p.Cys140=	synonymous_variant	3/5	1	NM_005666.4	P2	P36980-1

Frequencies

GnomAD3 genomes

AF:

0.228

AC:

34534

AN:

151696

Hom.:

5497

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0632

Gnomad AMI

AF:

0.132

Gnomad AMR

AF:

0.386

Gnomad ASJ

AF:

0.302

Gnomad EAS

AF:

0.717

Gnomad SAS

AF:

0.327

Gnomad FIN

AF:

0.305

Gnomad MID

AF:

0.174

Gnomad NFE

AF:

0.233

Gnomad OTH

AF:

0.249

GnomAD3 exomes

AF:

0.313

AC:

78565

AN:

251184

Hom.:

15759

AF XY:

0.305

AC XY:

41363

AN XY:

135744

show subpopulations

Gnomad AFR exome

AF:

0.0582

Gnomad AMR exome

AF:

0.510

Gnomad ASJ exome

AF:

0.297

Gnomad EAS exome

AF:

0.727

Gnomad SAS exome

AF:

0.292

Gnomad FIN exome

AF:

0.305

Gnomad NFE exome

AF:

0.233

Gnomad OTH exome

AF:

0.277

GnomAD4 exome

AF:

0.255

AC:

372475

AN:

1461414

Hom.:

55096

Cov.:

AF XY:

0.255

AC XY:

185586

AN XY:

727014

show subpopulations

Gnomad4 AFR exome

AF:

0.0505

Gnomad4 AMR exome

AF:

0.499

Gnomad4 ASJ exome

AF:

0.290

Gnomad4 EAS exome

AF:

0.701

Gnomad4 SAS exome

AF:

0.292

Gnomad4 FIN exome

AF:

0.299

Gnomad4 NFE exome

AF:

0.229

Gnomad4 OTH exome

AF:

0.265

GnomAD4 genome

AF:

0.228

AC:

34541

AN:

151810

Hom.:

5503

Cov.:

AF XY:

0.238

AC XY:

17687

AN XY:

74200

show subpopulations

Gnomad4 AFR

AF:

0.0630

Gnomad4 AMR

AF:

0.387

Gnomad4 ASJ

AF:

0.302

Gnomad4 EAS

AF:

0.717

Gnomad4 SAS

AF:

0.328

Gnomad4 FIN

AF:

0.305

Gnomad4 NFE

AF:

0.233

Gnomad4 OTH

AF:

0.248

Alfa

AF:

0.218

Hom.:

3770

Bravo

AF:

0.231

Asia WGS

AF:

0.505

AC:

1753

AN:

3478

EpiCase

AF:

0.233

EpiControl

AF:

0.230

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Nov 10, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.88

CADD

Benign

DANN

Benign

0.56

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.43

Details are displayed if max score is > 0.2

DS_DG_spliceai

0.43

Position offset: -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