dbSNP rs3790414: CFHR2:c.430+141T>A (chr1-196951169-T-A) – ACMG Classification: Benign (-20 pts)

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_005666.4(CFHR2):c.430+141T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.248 in 1,059,830 control chromosomes in the GnomAD database, including 39,375 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.26 ( 6293 hom., cov: 32)

Exomes 𝑓: 0.24 ( 33082 hom. )

Consequence

CFHR2
NM_005666.4 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.898

Publications

10 publications found

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 was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.93).

BP6

Variant 1-196951169-T-A is Benign according to our data. Variant chr1-196951169-T-A is described in ClinVar as [Benign]. Clinvar id is 1288915.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.696 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CFHR2	NM_005666.4 link	c.430+141T>A		intron_variant	Intron 3 of 4	ENST00000367415.8	NP_005657.1	P36980-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CFHR2	ENST00000367415.8 link	c.430+141T>A		intron_variant	Intron 3 of 4	1	NM_005666.4	ENSP00000356385.4		P36980-1

Frequencies

GnomAD3 genomes

AF:

0.264

AC:

40140

AN:

151996

Hom.:

6289

Cov.:

show subpopulations

Gnomad AFR

AF:

0.187

Gnomad AMI

AF:

0.132

Gnomad AMR

AF:

0.405

Gnomad ASJ

AF:

0.309

Gnomad EAS

AF:

0.715

Gnomad SAS

AF:

0.331

Gnomad FIN

AF:

0.304

Gnomad MID

AF:

0.197

Gnomad NFE

AF:

0.234

Gnomad OTH

AF:

0.275

GnomAD4 exome

AF:

0.245

AC:

222256

AN:

907716

Hom.:

33082

AF XY:

0.247

AC XY:

112637

AN XY:

456346

show subpopulations

African (AFR)

AF:

0.183

AC:

3893

AN:

21254

American (AMR)

AF:

0.461

AC:

10322

AN:

22386

Ashkenazi Jewish (ASJ)

AF:

0.286

AC:

4932

AN:

17224

East Asian (EAS)

AF:

0.697

AC:

22876

AN:

32812

South Asian (SAS)

AF:

0.287

AC:

15430

AN:

53708

European-Finnish (FIN)

AF:

0.287

AC:

11254

AN:

39244

Middle Eastern (MID)

AF:

0.185

AC:

631

AN:

3404

European-Non Finnish (NFE)

AF:

0.210

AC:

142167

AN:

676824

Other (OTH)

AF:

0.263

AC:

10751

AN:

40860

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.483

Heterozygous variant carriers

7367

14733

22100

29466

36833

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.264

AC:

40154

AN:

152114

Hom.:

6293

Cov.:

AF XY:

0.274

AC XY:

20408

AN XY:

74374

show subpopulations

African (AFR)

AF:

0.186

AC:

7735

AN:

41514

American (AMR)

AF:

0.406

AC:

6195

AN:

15272

Ashkenazi Jewish (ASJ)

AF:

0.309

AC:

1073

AN:

3472

East Asian (EAS)

AF:

0.715

AC:

3697

AN:

5172

South Asian (SAS)

AF:

0.331

AC:

1597

AN:

4822

European-Finnish (FIN)

AF:

0.304

AC:

3217

AN:

10572

Middle Eastern (MID)

AF:

0.192

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.234

AC:

15886

AN:

67972

Other (OTH)

AF:

0.273

AC:

578

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1433

2865

4298

5730

7163

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.241

Hom.:

564

Bravo

AF:

0.272

Asia WGS

AF:

0.512

AC:

1776

AN:

3472

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Nov 10, 2018

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.93

CADD

Benign

0.86

(source)

DANN

Benign

0.29

PhyloP100

-0.90

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

Publications

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rs3790414

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over