Genetic Variant CFHR2:c.-65C>G (chr1-196943816-C-G) – 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.-65C>G variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.052 ( 49 hom., cov: 4)

Exomes 𝑓: 0.065 ( 916 hom. )

Failed GnomAD Quality Control

Consequence

CFHR2
NM_005666.4 5_prime_UTR

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.443

Publications

0 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:

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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=-0.95).

BP6

Variant 1-196943816-C-G is Benign according to our data. Variant chr1-196943816-C-G is described in ClinVar as Benign. ClinVar VariationId is 1288324.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAdExome4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.0878 is higher than 0.05.

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

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
CFHR2	NM_005666.4	MANE Select	c.-65C>G	5_prime_UTR	Exon 1 of 5	NP_005657.1	P36980-1
CFHR2	NM_001410924.1		c.-65C>G	5_prime_UTR	Exon 1 of 4	NP_001397853.1	A0A3B3IRW0
CFHR2	NM_001312672.1		c.-65C>G	5_prime_UTR	Exon 1 of 3	NP_001299601.1	A0A3B3IS28

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
CFHR2	ENST00000367415.8	TSL:1 MANE Select	c.-65C>G	5_prime_UTR	Exon 1 of 5	ENSP00000356385.4	P36980-1
CFHR2	ENST00000367421.5	TSL:1	c.-65C>G	5_prime_UTR	Exon 1 of 6	ENSP00000356391.4	A0A3B3IQ51
CFHR2	ENST00000884518.1		c.-65C>G	5_prime_UTR	Exon 1 of 6	ENSP00000554577.1

Frequencies

GnomAD3 genomes

AF:

0.0518

AC:

913

AN:

17638

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0197

Gnomad AMI

AF:

0.188

Gnomad AMR

AF:

0.0580

Gnomad ASJ

AF:

0.0259

Gnomad EAS

AF:

0.0418

Gnomad SAS

AF:

0.0966

Gnomad FIN

AF:

0.0341

Gnomad MID

AF:

0.0349

Gnomad NFE

AF:

0.0565

Gnomad OTH

AF:

0.0282

GnomAD4 exome

AF:

0.0649

AC:

13112

AN:

201890

Hom.:

916

Cov.:

AF XY:

0.0658

AC XY:

7088

AN XY:

107784

show subpopulations

African (AFR)

AF:

0.0183

AC:

AN:

3600

American (AMR)

AF:

0.0926

AC:

963

AN:

10398

Ashkenazi Jewish (ASJ)

AF:

0.0301

AC:

152

AN:

5046

East Asian (EAS)

AF:

0.0630

AC:

845

AN:

13418

South Asian (SAS)

AF:

0.0843

AC:

2443

AN:

28996

European-Finnish (FIN)

AF:

0.0485

AC:

513

AN:

10578

Middle Eastern (MID)

AF:

0.0414

AC:

AN:

652

European-Non Finnish (NFE)

AF:

0.0632

AC:

7495

AN:

118502

Other (OTH)

AF:

0.0568

AC:

608

AN:

10700

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

416

832

1249

1665

2081

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

136

204

272

340

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.0519

AC:

915

AN:

17632

Hom.:

Cov.:

AF XY:

0.0537

AC XY:

410

AN XY:

7640

show subpopulations

African (AFR)

AF:

0.0201

AC:

AN:

1886

American (AMR)

AF:

0.0579

AC:

102

AN:

1762

Ashkenazi Jewish (ASJ)

AF:

0.0259

AC:

AN:

540

East Asian (EAS)

AF:

0.0426

AC:

AN:

1408

South Asian (SAS)

AF:

0.0948

AC:

AN:

580

European-Finnish (FIN)

AF:

0.0341

AC:

AN:

850

Middle Eastern (MID)

AF:

0.0395

AC:

AN:

European-Non Finnish (NFE)

AF:

0.0565

AC:

570

AN:

10090

Other (OTH)

AF:

0.0323

AC:

AN:

248

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.513

Heterozygous variant carriers

113

151

189

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00347

Hom.:

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.95

CADD

Benign

1.7

(source)

DANN

Benign

0.36

PhyloP100

-0.44

PromoterAI

-0.024

Neutral

(source)

Mutation Taster

=300/0

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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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over