rs385390

Positions:

• chr1-196774797-A-C
• chr1-196774797-A-G

Variant summary

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

The ENST00000696032.1(ENSG00000289697):​c.3581-4365A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.239 in 1,144,398 control chromosomes in the GnomAD database, including 59,010 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.28 (10829 hom., cov: 24)
  • Exomes 𝑓: 0.23 (48181 hom.)
• Consequence: ENSG00000289697 ENST00000696032.1 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.324

Genes affected

ENSG00000289697 (HGNC:):

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=-0.93).
• BP6: Variant 1-196774797-A-C is Benign according to our data. Variant chr1-196774797-A-C is described in ClinVar as [Benign]. Clinvar id is 1233740.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.489 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CFHR3	NM_021023.6	c.-90A>C		upstream_gene_variant		ENST00000367425.9	NP_066303.2
CFHR3	NM_001166624.2	c.-90A>C		upstream_gene_variant			NP_001160096.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ENSG00000289697	ENST00000696032.1	c.3581-4365A>C		intron_variant				ENSP00000512341.1
CFHR3	ENST00000367425.9	c.-90A>C		upstream_gene_variant		1	NM_021023.6	ENSP00000356395.5

Frequencies

GnomAD3 genomes AF: 0.280 AC: 37959 AN: 135512 Hom.: 10813 Cov.: 24

Gnomad AFR AF: 0.419

Gnomad AMI AF: 0.283

Gnomad AMR AF: 0.310

Gnomad ASJ AF: 0.196

Gnomad EAS AF: 0.505

Gnomad SAS AF: 0.217

Gnomad FIN AF: 0.162

Gnomad MID AF: 0.295

Gnomad NFE AF: 0.212

Gnomad OTH AF: 0.275

GnomAD4 exome AF: 0.233 AC: 235332 AN: 1008760 Hom.: 48181 Cov.: 14 AF XY: 0.230 AC XY: 118325 AN XY: 513554

Gnomad4 AFR exome AF: 0.426

Gnomad4 AMR exome AF: 0.409

Gnomad4 ASJ exome AF: 0.204

Gnomad4 EAS exome AF: 0.505

Gnomad4 SAS exome AF: 0.208

Gnomad4 FIN exome AF: 0.160

Gnomad4 NFE exome AF: 0.212

Gnomad4 OTH exome AF: 0.245

GnomAD4 genome AF: 0.280 AC: 37994 AN: 135638 Hom.: 10829 Cov.: 24 AF XY: 0.279 AC XY: 18444 AN XY: 66056

Gnomad4 AFR AF: 0.419

Gnomad4 AMR AF: 0.310

Gnomad4 ASJ AF: 0.196

Gnomad4 EAS AF: 0.506

Gnomad4 SAS AF: 0.217

Gnomad4 FIN AF: 0.162

Gnomad4 NFE AF: 0.212

Gnomad4 OTH AF: 0.273

Alfa AF: 0.259 Hom.: 1112

Asia WGS AF: 0.301 AC: 979 AN: 3248

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

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	2.9
DANN	Benign	0.30

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: rs385390; hg19: chr1-196743927; COSMIC: COSV66403242; COSMIC: COSV66403242;