1-196797447-T-C

Variant names:

• chr1-196797447-T-C
• rs644598
• ENST00000907750.1:c.*3934T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000907750.1(CFHR3):​c.*3934T>C variant causes a downstream gene change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.262 in 131,812 control chromosomes in the GnomAD database, including 9,273 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 0.26 (9273 hom., cov: 22)
• Consequence: CFHR3 ENST00000907750.1 downstream_gene
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.491
• Publications: 0 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)

ACMG classification

Our verdict: Benign. The variant received -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 = 0.48 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000907750.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
There are no transcript annotations for this variant.

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CFHR3	ENST00000907750.1		c.*3934T>C		downstream_gene	N/A	ENSP00000577809.1
	CFHR3	ENST00000907751.1		c.*3934T>C		downstream_gene	N/A	ENSP00000577810.1

Frequencies

GnomAD3 genomes AF: 0.262 AC: 34500 AN: 131682 Hom.: 9258 Cov.: 22

Gnomad AFR AF: 0.400

Gnomad AMI AF: 0.283

Gnomad AMR AF: 0.290

Gnomad ASJ AF: 0.189

Gnomad EAS AF: 0.496

Gnomad SAS AF: 0.193

Gnomad FIN AF: 0.133

Gnomad MID AF: 0.271

Gnomad NFE AF: 0.200

Gnomad OTH AF: 0.243

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.262 AC: 34533 AN: 131812 Hom.: 9273 Cov.: 22 AF XY: 0.258 AC XY: 16543 AN XY: 64044

African (AFR) AF: 0.400 AC: 12049 AN: 30126

American (AMR) AF: 0.289 AC: 3964 AN: 13700

Ashkenazi Jewish (ASJ) AF: 0.189 AC: 590 AN: 3124

East Asian (EAS) AF: 0.496 AC: 2455 AN: 4948

South Asian (SAS) AF: 0.192 AC: 734 AN: 3814

European-Finnish (FIN) AF: 0.133 AC: 1308 AN: 9822

Middle Eastern (MID) AF: 0.272 AC: 68 AN: 250

European-Non Finnish (NFE) AF: 0.200 AC: 12691 AN: 63380

Other (OTH) AF: 0.241 AC: 427 AN: 1774

Alfa AF: 0.241 Hom.: 991

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	11
DANN	Benign	0.76
PhyloP100		0.49

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs644598; hg19: chr1-196766577;