rs426736

Variant names:

• chr1-196791287-A-G
• rs426736
• NM_021023.6:c.796+1060A>G

Your query was ambiguous. Multiple possible variants found:

• chr1-196791287-A-G
• chr1-196791287-A-T

Variant summary

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

The NM_021023.6(CFHR3):​c.796+1060A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.281 in 135,238 control chromosomes in the GnomAD database, including 10,747 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 0.28 (10747 hom., cov: 24)
• Consequence: CFHR3 NM_021023.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.29
• Publications: 25 publications found

Genes affected

CFHR3 (HGNC:16980): (complement factor H related 3) The protein encoded by this gene is a secreted protein, which belongs to the complement factor H-related protein family. It binds to heparin, and may be involved in complement regulation. Mutations in this gene are associated with decreased risk of age-related macular degeneration, and with an increased risk of atypical hemolytic-uremic syndrome. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Oct 2011]

CFHR3 Gene-Disease associations (from GenCC):

• hemolytic uremic syndrome, atypical, susceptibility to, 1

  Inheritance: Unknown Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae)

ENSG00000289697 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.02).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.488 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_021023.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CFHR3	NM_021023.6	MANE Select	c.796+1060A>G		intron	N/A	NP_066303.2
	CFHR3	NM_001166624.2		c.613+1060A>G		intron	N/A	NP_001160096.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CFHR3	ENST00000367425.9	TSL:1 MANE Select	c.796+1060A>G		intron	N/A	ENSP00000356395.5
	ENSG00000289697	ENST00000696032.1		c.4318+1060A>G		intron	N/A	ENSP00000512341.1
	CFHR3	ENST00000391985.7	TSL:2	c.613+1060A>G		intron	N/A	ENSP00000375845.3

Frequencies

GnomAD3 genomes AF: 0.281 AC: 37935 AN: 135108 Hom.: 10733 Cov.: 24

Gnomad AFR AF: 0.432

Gnomad AMI AF: 0.283

Gnomad AMR AF: 0.304

Gnomad ASJ AF: 0.196

Gnomad EAS AF: 0.504

Gnomad SAS AF: 0.214

Gnomad FIN AF: 0.161

Gnomad MID AF: 0.283

Gnomad NFE AF: 0.211

Gnomad OTH AF: 0.265

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

GnomAD4 genome AF: 0.281 AC: 37966 AN: 135238 Hom.: 10747 Cov.: 24 AF XY: 0.279 AC XY: 18356 AN XY: 65812

African (AFR) AF: 0.431 AC: 13762 AN: 31914

American (AMR) AF: 0.303 AC: 4256 AN: 14044

Ashkenazi Jewish (ASJ) AF: 0.196 AC: 621 AN: 3168

East Asian (EAS) AF: 0.504 AC: 2551 AN: 5060

South Asian (SAS) AF: 0.213 AC: 825 AN: 3866

European-Finnish (FIN) AF: 0.161 AC: 1614 AN: 10030

Middle Eastern (MID) AF: 0.287 AC: 74 AN: 258

European-Non Finnish (NFE) AF: 0.211 AC: 13525 AN: 64156

Other (OTH) AF: 0.263 AC: 487 AN: 1854

Alfa AF: 0.262 Hom.: 1120

Asia WGS AF: 0.300 AC: 977 AN: 3256

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	1.0
DANN	Benign	0.32
PhyloP100		-2.3
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: rs426736; hg19: chr1-196760417;