1-196789411-A-C

Position:

• chr1-196789411-A-C

Variant summary

Our verdict is Benign. Variant got -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

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 -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CFHR3	NM_021023.6	c.614-634A>C		intron_variant		ENST00000367425.9
CFHR3	NM_001166624.2	c.431-634A>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CFHR3	ENST00000471440.6	c.*581A>C		3_prime_UTR_variant	5/5	1
CFHR3	ENST00000367425.9	c.614-634A>C		intron_variant		1	NM_021023.6	P1
CFHR3	ENST00000391985.7	c.431-634A>C		intron_variant		2
CFHR3	ENST00000367427.7	c.*114+467A>C		intron_variant, NMD_transcript_variant		5

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

Gnomad4 AFR exome AF: 0.435

Gnomad4 AMR exome AF: 0.348

Gnomad4 ASJ exome AF: 0.209

Gnomad4 EAS exome AF: 0.558

Gnomad4 SAS exome AF: 0.208

Gnomad4 FIN exome AF: 0.196

Gnomad4 NFE exome AF: 0.206

Gnomad4 OTH exome AF: 0.235

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

Gnomad4 AFR AF: 0.435

Gnomad4 AMR AF: 0.302

Gnomad4 ASJ AF: 0.195

Gnomad4 EAS AF: 0.507

Gnomad4 SAS AF: 0.210

Gnomad4 FIN AF: 0.165

Gnomad4 NFE AF: 0.212

Gnomad4 OTH AF: 0.269

Alfa AF: 0.0749 Hom.: 168

Asia WGS AF: 0.300 AC: 969 AN: 3234

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.42
DANN	Benign	0.46

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: rs377298; hg19: chr1-196758541;