chr1-196789156-T-C

Variant names:

• chr1-196789156-T-C
• rs378283
• ENST00000471440.6:c.*326T>C

Variant summary

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

The ENST00000471440.6(CFHR3):​c.*326T>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 0.218 in 971,882 control chromosomes in the GnomAD database, including 46,505 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 (10933 hom., cov: 24)
  • Exomes 𝑓: 0.21 (35572 hom.)
• Consequence: CFHR3 ENST00000471440.6 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.631
• 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=-0.96).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.489 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CFHR3	NM_021023.6	MANE Select	c.613+758T>C		intron	N/A	NP_066303.2	Q02985-1
	CFHR3	NM_001166624.2		c.431-889T>C		intron	N/A	NP_001160096.1	Q02985-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CFHR3	ENST00000471440.6	TSL:1	c.*326T>C		3_prime_UTR	Exon 5 of 5	ENSP00000436258.1	Q6NSD3
	CFHR3	ENST00000367425.9	TSL:1 MANE Select	c.613+758T>C		intron	N/A	ENSP00000356395.5	Q02985-1
	ENSG00000289697	ENST00000696032.1		c.4135+758T>C		intron	N/A	ENSP00000512341.1	A0A8Q3SIA1

Frequencies

GnomAD3 genomes AF: 0.283 AC: 38314 AN: 135574 Hom.: 10920 Cov.: 24

Gnomad AFR AF: 0.436

Gnomad AMI AF: 0.288

Gnomad AMR AF: 0.302

Gnomad ASJ AF: 0.196

Gnomad EAS AF: 0.506

Gnomad SAS AF: 0.214

Gnomad FIN AF: 0.161

Gnomad MID AF: 0.302

Gnomad NFE AF: 0.212

Gnomad OTH AF: 0.268

GnomAD4 exome AF: 0.207 AC: 173434 AN: 836194 Hom.: 35572 Cov.: 13 AF XY: 0.206 AC XY: 80904 AN XY: 393078

African (AFR) AF: 0.420 AC: 5036 AN: 11986

American (AMR) AF: 0.315 AC: 1758 AN: 5586

Ashkenazi Jewish (ASJ) AF: 0.184 AC: 1295 AN: 7020

East Asian (EAS) AF: 0.489 AC: 4793 AN: 9804

South Asian (SAS) AF: 0.183 AC: 4184 AN: 22884

European-Finnish (FIN) AF: 0.142 AC: 883 AN: 6204

Middle Eastern (MID) AF: 0.212 AC: 341 AN: 1610

European-Non Finnish (NFE) AF: 0.200 AC: 148513 AN: 741396

Other (OTH) AF: 0.223 AC: 6631 AN: 29704

GnomAD4 genome AF: 0.283 AC: 38342 AN: 135688 Hom.: 10933 Cov.: 24 AF XY: 0.281 AC XY: 18566 AN XY: 66034

African (AFR) AF: 0.435 AC: 14055 AN: 32294

American (AMR) AF: 0.302 AC: 4227 AN: 14008

Ashkenazi Jewish (ASJ) AF: 0.196 AC: 623 AN: 3180

East Asian (EAS) AF: 0.506 AC: 2554 AN: 5050

South Asian (SAS) AF: 0.214 AC: 834 AN: 3900

European-Finnish (FIN) AF: 0.161 AC: 1628 AN: 10084

Middle Eastern (MID) AF: 0.314 AC: 76 AN: 242

European-Non Finnish (NFE) AF: 0.212 AC: 13599 AN: 64194

Other (OTH) AF: 0.265 AC: 493 AN: 1858

Alfa AF: 0.0754 Hom.: 172

Asia WGS AF: 0.300 AC: 974 AN: 3250

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	3.2
DANN	Benign	0.72
PhyloP100		-0.63
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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs378283;

hg19: chr1-196758286;