rs1659384027

Variant names:

• chr1-196943876-C-G
• rs1659384027
• NM_005666.4:c.-5C>G

Variant summary

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

The NM_005666.4(CFHR2):​c.-5C>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 Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.0 (0 hom., cov: 5)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: CFHR2 NM_005666.4 5_prime_UTR
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.228
• Publications: 0 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: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).

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.-5C>G		5_prime_UTR	Exon 1 of 5	NP_005657.1	P36980-1
	CFHR2	NM_001410924.1		c.-5C>G		5_prime_UTR	Exon 1 of 4	NP_001397853.1	A0A3B3IRW0
	CFHR2	NM_001312672.1		c.-5C>G		5_prime_UTR	Exon 1 of 3	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.-5C>G		5_prime_UTR	Exon 1 of 5	ENSP00000356385.4	P36980-1
	CFHR2	ENST00000367421.5	TSL:1	c.-5C>G		5_prime_UTR	Exon 1 of 6	ENSP00000356391.4	A0A3B3IQ51
	CFHR2	ENST00000473386.1	TSL:1	c.-5C>G		5_prime_UTR	Exon 1 of 3	ENSP00000497089.1	A0A3B3IS28

Frequencies

GnomAD3 genomes AF: 0.00 AC: 0 AN: 28828 Hom.: 0 Cov.: 5

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: AC0;AS_VQSR AF: 0.00 AC: 0 AN: 291918 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 154408

African (AFR) AF: 0.00 AC: 0 AN: 5144

American (AMR) AF: 0.00 AC: 0 AN: 13660

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 7714

East Asian (EAS) AF: 0.00 AC: 0 AN: 23028

South Asian (SAS) AF: 0.00 AC: 0 AN: 31566

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 20364

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 1032

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 173378

Other (OTH) AF: 0.00 AC: 0 AN: 16032

GnomAD4 genome Data not reliable, filtered out with message: AC0;AS_VQSR AF: 0.00 AC: 0 AN: 28828 Hom.: 0 Cov.: 5 AF XY: 0.00 AC XY: 0 AN XY: 12774

African (AFR) AF: 0.00 AC: 0 AN: 3176

American (AMR) AF: 0.00 AC: 0 AN: 2626

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 920

East Asian (EAS) AF: 0.00 AC: 0 AN: 1788

South Asian (SAS) AF: 0.00 AC: 0 AN: 756

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 1290

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 90

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 17436

Other (OTH) AF: 0.00 AC: 0 AN: 370

Alfa AF: 0.00 Hom.: 0

ClinVar

ClinVar submissions as Germline

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	2.4
DANN	Benign	0.56
PhyloP100		-0.23
PromoterAI		0.022	Neutral

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: rs1659384027; hg19: chr1-196913006;