1-196789156-T-C

Position:

• chr1-196789156-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000367425.9(CFHR3):​c.613+758T>C variant causes a intron 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 ENST00000367425.9 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.631

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=-0.96).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.489 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CFHR3	NM_021023.6	c.613+758T>C		intron_variant		ENST00000367425.9	NP_066303.2
CFHR3	NM_001166624.2	c.431-889T>C		intron_variant			NP_001160096.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CFHR3	ENST00000471440.6	c.*326T>C		3_prime_UTR_variant	5/5	1		ENSP00000436258
CFHR3	ENST00000367425.9	c.613+758T>C		intron_variant		1	NM_021023.6	ENSP00000356395	P1
CFHR3	ENST00000391985.7	c.431-889T>C		intron_variant		2		ENSP00000375845
CFHR3	ENST00000367427.7	c.*114+212T>C		intron_variant, NMD_transcript_variant		5		ENSP00000356397

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

Gnomad4 AFR exome AF: 0.420

Gnomad4 AMR exome AF: 0.315

Gnomad4 ASJ exome AF: 0.184

Gnomad4 EAS exome AF: 0.489

Gnomad4 SAS exome AF: 0.183

Gnomad4 FIN exome AF: 0.142

Gnomad4 NFE exome AF: 0.200

Gnomad4 OTH exome AF: 0.223

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

Gnomad4 AFR AF: 0.435

Gnomad4 AMR AF: 0.302

Gnomad4 ASJ AF: 0.196

Gnomad4 EAS AF: 0.506

Gnomad4 SAS AF: 0.214

Gnomad4 FIN AF: 0.161

Gnomad4 NFE AF: 0.212

Gnomad4 OTH AF: 0.265

Alfa AF: 0.0754 Hom.: 172

Asia WGS AF: 0.300 AC: 974 AN: 3250

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

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

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: rs378283; hg19: chr1-196758286;