rs377298

Variant names:

• chr1-196789411-A-C
• rs377298
• ENST00000471440.6:c.*581A>C

Your query was ambiguous. Multiple possible variants found:

• chr1-196789411-A-C
• chr1-196789411-A-G
• chr1-196789411-A-T

Variant summary

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

The ENST00000471440.6(CFHR3):​c.*581A>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.225 in 888,710 control chromosomes in the GnomAD database, including 44,115 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 (10883 hom., cov: 24)
  • Exomes 𝑓: 0.21 (33232 hom.)
• Consequence: CFHR3 ENST00000471440.6 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.665
• Publications: 1 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=-0.94).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.49 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000471440.6. 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.614-634A>C		intron	N/A	NP_066303.2
	CFHR3	NM_001166624.2		c.431-634A>C		intron	N/A	NP_001160096.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CFHR3	ENST00000471440.6	TSL:1	c.*581A>C		3_prime_UTR	Exon 5 of 5	ENSP00000436258.1
	CFHR3	ENST00000367425.9	TSL:1 MANE Select	c.614-634A>C		intron	N/A	ENSP00000356395.5
	ENSG00000289697	ENST00000696032.1		c.4136-634A>C		intron	N/A	ENSP00000512341.1

Frequencies

GnomAD3 genomes AF: 0.283 AC: 38210 AN: 135146 Hom.: 10870 Cov.: 24

Gnomad AFR AF: 0.435

Gnomad AMI AF: 0.287

Gnomad AMR AF: 0.303

Gnomad ASJ AF: 0.195

Gnomad EAS AF: 0.506

Gnomad SAS AF: 0.210

Gnomad FIN AF: 0.165

Gnomad MID AF: 0.285

Gnomad NFE AF: 0.212

Gnomad OTH AF: 0.272

GnomAD4 exome AF: 0.215 AC: 161917 AN: 753456 Hom.: 33232 Cov.: 10 AF XY: 0.214 AC XY: 75715 AN XY: 353116

African (AFR) AF: 0.435 AC: 4685 AN: 10774

American (AMR) AF: 0.348 AC: 1208 AN: 3470

Ashkenazi Jewish (ASJ) AF: 0.209 AC: 1094 AN: 5228

East Asian (EAS) AF: 0.558 AC: 4373 AN: 7838

South Asian (SAS) AF: 0.208 AC: 3035 AN: 14588

European-Finnish (FIN) AF: 0.196 AC: 475 AN: 2422

Middle Eastern (MID) AF: 0.228 AC: 302 AN: 1322

European-Non Finnish (NFE) AF: 0.206 AC: 140745 AN: 682250

Other (OTH) AF: 0.235 AC: 6000 AN: 25564

GnomAD4 genome AF: 0.283 AC: 38239 AN: 135254 Hom.: 10883 Cov.: 24 AF XY: 0.281 AC XY: 18513 AN XY: 65850

African (AFR) AF: 0.435 AC: 13967 AN: 32118

American (AMR) AF: 0.302 AC: 4233 AN: 14012

Ashkenazi Jewish (ASJ) AF: 0.195 AC: 616 AN: 3154

East Asian (EAS) AF: 0.507 AC: 2569 AN: 5072

South Asian (SAS) AF: 0.210 AC: 812 AN: 3864

European-Finnish (FIN) AF: 0.165 AC: 1652 AN: 9994

Middle Eastern (MID) AF: 0.292 AC: 70 AN: 240

European-Non Finnish (NFE) AF: 0.212 AC: 13576 AN: 64092

Other (OTH) AF: 0.269 AC: 490 AN: 1824

Alfa AF: 0.0749 Hom.: 168

Asia WGS AF: 0.300 AC: 969 AN: 3234

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.42
DANN	Benign	0.46
PhyloP100		-0.67
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: rs377298; hg19: chr1-196758541;