Genetic Variant NM_005666.4:c.58+129C>T (chr1-196944067-C-T) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_005666.4(CFHR2):c.58+129C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.0 ( 0 hom., cov: 15)

Exomes 𝑓: 0.0000045 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

CFHR2
NM_005666.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.258

Publications

2 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: Likely_benign. The variant received -4 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.91).

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.58+129C>T	intron	N/A	NP_005657.1	P36980-1
CFHR2	NM_001410924.1		c.58+129C>T	intron	N/A	NP_001397853.1	A0A3B3IRW0
CFHR2	NM_001312672.1		c.58+129C>T	intron	N/A	NP_001299601.1	A0A3B3IS28

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
CFHR2	ENST00000367415.8	TSL:1 MANE Select	c.58+129C>T	intron	N/A	ENSP00000356385.4	P36980-1
CFHR2	ENST00000367421.5	TSL:1	c.58+129C>T	intron	N/A	ENSP00000356391.4	A0A3B3IQ51
CFHR2	ENST00000473386.1	TSL:1	c.58+129C>T	intron	N/A	ENSP00000497089.1	A0A3B3IS28

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

AN:

96188

Hom.:

Cov.:

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.00000454

AC:

AN:

220122

Hom.:

AF XY:

0.00000855

AC XY:

AN XY:

117006

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

3080

American (AMR)

AF:

0.00

AC:

AN:

11044

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

5328

East Asian (EAS)

AF:

0.0000544

AC:

AN:

18376

South Asian (SAS)

AF:

0.00

AC:

AN:

24590

European-Finnish (FIN)

AF:

0.00

AC:

AN:

20206

Middle Eastern (MID)

AF:

0.00

AC:

AN:

650

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

125400

Other (OTH)

AF:

0.00

AC:

AN:

11448

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

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

GnomAD4 genome

Data not reliable, filtered out with message: AC0;AS_VQSR

AF:

0.00

AC:

AN:

96188

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

46522

African (AFR)

AF:

0.00

AC:

AN:

16444

American (AMR)

AF:

0.00

AC:

AN:

9868

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2404

East Asian (EAS)

AF:

0.00

AC:

AN:

4050

South Asian (SAS)

AF:

0.00

AC:

AN:

2914

European-Finnish (FIN)

AF:

0.00

AC:

AN:

7692

Middle Eastern (MID)

AF:

0.00

AC:

AN:

190

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

50586

Other (OTH)

AF:

0.00

AC:

AN:

1246

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.91

CADD

Benign

3.5

(source)

DANN

Benign

0.68

PhyloP100

-0.26

PromoterAI

-0.0047

Neutral

(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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over