rs12066959

Variant names:

• chr1-196948769-G-A
• rs12066959
• NM_005666.4:c.59-686G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_005666.4(CFHR2):​c.59-686G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.265 in 151,670 control chromosomes in the GnomAD database, including 6,304 homozygotes. 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 0.26 (6304 hom., cov: 32)
• Consequence: CFHR2 NM_005666.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.94
• Publications: 4 publications found

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]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.04).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.701 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CFHR2	NM_005666.4	MANE Select	c.59-686G>A		intron	N/A	NP_005657.1	P36980-1
	CFHR2	NM_001410924.1		c.59-2083G>A		intron	N/A	NP_001397853.1	A0A3B3IRW0
	CFHR2	NM_001312672.1		c.58+4831G>A		intron	N/A	NP_001299601.1	A0A3B3IS28

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CFHR2	ENST00000367415.8	TSL:1 MANE Select	c.59-686G>A		intron	N/A	ENSP00000356385.4	P36980-1
	CFHR2	ENST00000367421.5	TSL:1	c.313+216G>A		intron	N/A	ENSP00000356391.4	A0A3B3IQ51
	CFHR2	ENST00000473386.1	TSL:1	c.58+4831G>A		intron	N/A	ENSP00000497089.1	A0A3B3IS28

Frequencies

GnomAD3 genomes AF: 0.265 AC: 40104 AN: 151556 Hom.: 6300 Cov.: 32

Gnomad AFR AF: 0.187

Gnomad AMI AF: 0.132

Gnomad AMR AF: 0.405

Gnomad ASJ AF: 0.309

Gnomad EAS AF: 0.720

Gnomad SAS AF: 0.331

Gnomad FIN AF: 0.306

Gnomad MID AF: 0.197

Gnomad NFE AF: 0.234

Gnomad OTH AF: 0.276

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.265 AC: 40118 AN: 151670 Hom.: 6304 Cov.: 32 AF XY: 0.275 AC XY: 20376 AN XY: 74098

African (AFR) AF: 0.187 AC: 7704 AN: 41288

American (AMR) AF: 0.406 AC: 6182 AN: 15224

Ashkenazi Jewish (ASJ) AF: 0.309 AC: 1072 AN: 3472

East Asian (EAS) AF: 0.720 AC: 3717 AN: 5162

South Asian (SAS) AF: 0.331 AC: 1590 AN: 4804

European-Finnish (FIN) AF: 0.306 AC: 3202 AN: 10470

Middle Eastern (MID) AF: 0.192 AC: 56 AN: 292

European-Non Finnish (NFE) AF: 0.234 AC: 15897 AN: 67938

Other (OTH) AF: 0.274 AC: 578 AN: 2108

Alfa AF: 0.239 Hom.: 587

Bravo AF: 0.272

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.11
DANN	Benign	0.59
PhyloP100		-1.9
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs12066959; hg19: chr1-196917899;