1-196774834-C-A

Position:

• chr1-196774834-C-A

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The ENST00000471440.6(CFHR3):​c.-53C>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.232 in 1,397,832 control chromosomes in the GnomAD database, including 74,714 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.25 (9355 hom., cov: 24)
  • Exomes 𝑓: 0.23 (65359 hom.)
• Consequence: CFHR3 ENST00000471440.6 5_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.63

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]

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BP6: Variant 1-196774834-C-A is Benign according to our data. Variant chr1-196774834-C-A is described in ClinVar as [Benign]. Clinvar id is 1275873.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.49 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CFHR3	NM_021023.6			upstream_gene_variant		ENST00000367425.9
CFHR3	NM_001166624.2			upstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CFHR3	ENST00000471440.6	c.-53C>A		5_prime_UTR_variant	1/5	1
CFHR3	ENST00000391985.7	c.-53C>A		5_prime_UTR_variant	1/5	2
CFHR3	ENST00000367427.7	c.-53C>A		5_prime_UTR_variant, NMD_transcript_variant	1/7	5
CFHR3	ENST00000367425.9			upstream_gene_variant		1	NM_021023.6	P1

Frequencies

GnomAD3 genomes AF: 0.255 AC: 34568 AN: 135564 Hom.: 9344 Cov.: 24

Gnomad AFR AF: 0.316

Gnomad AMI AF: 0.289

Gnomad AMR AF: 0.304

Gnomad ASJ AF: 0.198

Gnomad EAS AF: 0.506

Gnomad SAS AF: 0.220

Gnomad FIN AF: 0.163

Gnomad MID AF: 0.296

Gnomad NFE AF: 0.212

Gnomad OTH AF: 0.255

GnomAD4 exome AF: 0.229 AC: 289219 AN: 1262138 Hom.: 65359 Cov.: 22 AF XY: 0.227 AC XY: 143343 AN XY: 632258

Gnomad4 AFR exome AF: 0.320

Gnomad4 AMR exome AF: 0.405

Gnomad4 ASJ exome AF: 0.202

Gnomad4 EAS exome AF: 0.507

Gnomad4 SAS exome AF: 0.207

Gnomad4 FIN exome AF: 0.161

Gnomad4 NFE exome AF: 0.213

Gnomad4 OTH exome AF: 0.239

GnomAD4 genome AF: 0.255 AC: 34589 AN: 135694 Hom.: 9355 Cov.: 24 AF XY: 0.254 AC XY: 16788 AN XY: 66016

Gnomad4 AFR AF: 0.316

Gnomad4 AMR AF: 0.304

Gnomad4 ASJ AF: 0.198

Gnomad4 EAS AF: 0.506

Gnomad4 SAS AF: 0.220

Gnomad4 FIN AF: 0.163

Gnomad4 NFE AF: 0.212

Gnomad4 OTH AF: 0.253

Alfa AF: 0.232 Hom.: 966

Asia WGS AF: 0.295 AC: 960 AN: 3254

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Nov 10, 2018	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.11
DANN	Benign	0.59

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

Publications

LitVar

Other links and lift over

dbSNP: rs446868; hg19: chr1-196743964;