ENST00000471440.6:c.*326T>A

Variant names:

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

Variant summary

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

The ENST00000471440.6(CFHR3):​c.*326T>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. 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 0.0 (0 hom., cov: 24)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• 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: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).

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.613+758T>A		intron	N/A	NP_066303.2
	CFHR3	NM_001166624.2		c.431-889T>A		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.*326T>A		3_prime_UTR	Exon 5 of 5	ENSP00000436258.1
	CFHR3	ENST00000367425.9	TSL:1 MANE Select	c.613+758T>A		intron	N/A	ENSP00000356395.5
	ENSG00000289697	ENST00000696032.1		c.4135+758T>A		intron	N/A	ENSP00000512341.1

Frequencies

GnomAD3 genomes AF: 0.00 AC: 0 AN: 135628 Hom.: 0 Cov.: 24

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 AF: 0.00 AC: 0 AN: 838058 Hom.: 0 Cov.: 13 AF XY: 0.00 AC XY: 0 AN XY: 393980

African (AFR) AF: 0.00 AC: 0 AN: 12026

American (AMR) AF: 0.00 AC: 0 AN: 5616

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 7036

East Asian (EAS) AF: 0.00 AC: 0 AN: 9850

South Asian (SAS) AF: 0.00 AC: 0 AN: 22950

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 6228

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 1614

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 742958

Other (OTH) AF: 0.00 AC: 0 AN: 29780

GnomAD4 genome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 135628 Hom.: 0 Cov.: 24 AF XY: 0.00 AC XY: 0 AN XY: 65940

African (AFR) AF: 0.00 AC: 0 AN: 32190

American (AMR) AF: 0.00 AC: 0 AN: 14002

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3180

East Asian (EAS) AF: 0.00 AC: 0 AN: 5066

South Asian (SAS) AF: 0.00 AC: 0 AN: 3906

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10084

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 258

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 64224

Other (OTH) AF: 0.00 AC: 0 AN: 1840

Alfa AF: 0.00 Hom.: 172

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	2.7
DANN	Benign	0.63
PhyloP100		-0.63

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: rs378283; hg19: chr1-196758286;