chr1-196949611-G-A

Variant names:

• chr1-196949611-G-A
• rs79351096
• NM_005666.4:c.215G>A

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_005666.4(CFHR2):​c.215G>A​(p.Cys72Tyr) variant causes a missense change. The variant allele was found at a frequency of 0.0251 in 1,613,888 control chromosomes in the GnomAD database, including 800 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.021 (69 hom., cov: 33)
  • Exomes 𝑓: 0.026 (731 hom.)
• Consequence: CFHR2 NM_005666.4 missense
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 3.64
• Publications: 14 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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.002033323).
• BP6: Variant 1-196949611-G-A is Benign according to our data. Variant chr1-196949611-G-A is described in ClinVar as Benign. ClinVar VariationId is 1712442.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAdExome4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.0931 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.215G>A	p.Cys72Tyr	missense	Exon 2 of 5	NP_005657.1	P36980-1
	CFHR2	NM_001410924.1		c.59-1241G>A		intron	N/A	NP_001397853.1	A0A3B3IRW0
	CFHR2	NM_001312672.1		c.58+5673G>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.215G>A	p.Cys72Tyr	missense	Exon 2 of 5	ENSP00000356385.4	P36980-1
	CFHR2	ENST00000367421.5	TSL:1	c.470G>A	p.Cys157Tyr	missense	Exon 3 of 6	ENSP00000356391.4	A0A3B3IQ51
	CFHR2	ENST00000473386.1	TSL:1	c.58+5673G>A		intron	N/A	ENSP00000497089.1	A0A3B3IS28

Frequencies

GnomAD3 genomes AF: 0.0208 AC: 3162 AN: 152204 Hom.: 69 Cov.: 33

Gnomad AFR AF: 0.00494

Gnomad AMI AF: 0.163

Gnomad AMR AF: 0.0386

Gnomad ASJ AF: 0.0115

Gnomad EAS AF: 0.000577

Gnomad SAS AF: 0.0325

Gnomad FIN AF: 0.0295

Gnomad MID AF: 0.00949

Gnomad NFE AF: 0.0246

Gnomad OTH AF: 0.0129

GnomAD2 exomes AF: 0.0326 AC: 8182 AN: 251196 AF XY: 0.0298

Gnomad AFR exome AF: 0.00400

Gnomad AMR exome AF: 0.105

Gnomad ASJ exome AF: 0.0120

Gnomad EAS exome AF: 0.000217

Gnomad FIN exome AF: 0.0301

Gnomad NFE exome AF: 0.0229

Gnomad OTH exome AF: 0.0299

GnomAD4 exome AF: 0.0256 AC: 37386 AN: 1461566 Hom.: 731 Cov.: 31 AF XY: 0.0252 AC XY: 18294 AN XY: 727092

African (AFR) AF: 0.00394 AC: 132 AN: 33464

American (AMR) AF: 0.0955 AC: 4267 AN: 44674

Ashkenazi Jewish (ASJ) AF: 0.0124 AC: 324 AN: 26128

East Asian (EAS) AF: 0.0000504 AC: 2 AN: 39678

South Asian (SAS) AF: 0.0305 AC: 2627 AN: 86254

European-Finnish (FIN) AF: 0.0281 AC: 1501 AN: 53416

Middle Eastern (MID) AF: 0.00625 AC: 36 AN: 5762

European-Non Finnish (NFE) AF: 0.0245 AC: 27247 AN: 1111814

Other (OTH) AF: 0.0207 AC: 1250 AN: 60376

GnomAD4 genome AF: 0.0208 AC: 3163 AN: 152322 Hom.: 69 Cov.: 33 AF XY: 0.0210 AC XY: 1564 AN XY: 74494

African (AFR) AF: 0.00493 AC: 205 AN: 41582

American (AMR) AF: 0.0386 AC: 590 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.0115 AC: 40 AN: 3472

East Asian (EAS) AF: 0.000578 AC: 3 AN: 5190

South Asian (SAS) AF: 0.0327 AC: 158 AN: 4832

European-Finnish (FIN) AF: 0.0295 AC: 313 AN: 10608

Middle Eastern (MID) AF: 0.0102 AC: 3 AN: 294

European-Non Finnish (NFE) AF: 0.0246 AC: 1675 AN: 68026

Other (OTH) AF: 0.0128 AC: 27 AN: 2114

Alfa AF: 0.0211 Hom.: 80

Bravo AF: 0.0220

TwinsUK AF: 0.0216 AC: 80

ALSPAC AF: 0.0254 AC: 98

ESP6500AA AF: 0.00681 AC: 30

ESP6500EA AF: 0.0256 AC: 220

ExAC AF: 0.0295 AC: 3586

Asia WGS AF: 0.00924 AC: 32 AN: 3478

EpiCase AF: 0.0209

EpiControl AF: 0.0206

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	Atypical hemolytic-uremic syndrome (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.93
BayesDel_addAF	Benign	-0.24	T
BayesDel_noAF	Uncertain	-0.030
CADD	Benign	22
DANN	Benign	0.94
DEOGEN2	Benign	0.30	T
Eigen	Benign	0.18
Eigen_PC	Benign	-0.066
FATHMM_MKL	Benign	0.35	N
LIST_S2	Benign	0.78	T
MetaRNN	Benign	0.0020	T
MetaSVM	Uncertain	0.20	D
MutationAssessor	Pathogenic	3.1	M
PhyloP100		3.6
PrimateAI	Benign	0.46	T
PROVEAN	Pathogenic	-10	D
REVEL	Uncertain	0.42
Sift	Pathogenic	0.0	D
Sift4G	Pathogenic	0.0	D
Polyphen		1.0	D
Vest4		0.60
MPC		0.025
ClinPred		0.14	T
GERP RS		3.3
Varity_R		0.89
gMVP		0.83
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs79351096; hg19: chr1-196918741;