NM_021023.6:c.354C>T

Variant names:

• chr1-196779897-C-T
• rs144398879
• NM_021023.6:c.354C>T

Variant summary

Our verdict is Benign. The variant received -17 ACMG points: 0P and 17B. BP4_Strong BP6_Very_Strong BP7 BS2

The NM_021023.6(CFHR3):​c.354C>T​(p.Tyr118Tyr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000261 in 1,533,054 control chromosomes in the GnomAD database, including 76 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.00026 (6 hom., cov: 25)
  • Exomes 𝑓: 0.00026 (70 hom.)
• Consequence: CFHR3 NM_021023.6 synonymous
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -1.67
• Publications: 4 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)

ENSG00000289697 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -17 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BP6: Variant 1-196779897-C-T is Benign according to our data. Variant chr1-196779897-C-T is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 761758.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-1.66 with no splicing effect.
• BS2: High Homozygotes in GnomAd4 at 6 Unknown gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_021023.6. 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
	CFHR3	NM_021023.6	MANE Select	c.354C>T	p.Tyr118Tyr	synonymous	Exon 3 of 6	NP_066303.2	Q02985-1
	CFHR3	NM_001166624.2		c.354C>T	p.Tyr118Tyr	synonymous	Exon 3 of 5	NP_001160096.1	Q02985-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CFHR3	ENST00000367425.9	TSL:1 MANE Select	c.354C>T	p.Tyr118Tyr	synonymous	Exon 3 of 6	ENSP00000356395.5	Q02985-1
	ENSG00000289697	ENST00000696032.1		c.3876C>T	p.Tyr1292Tyr	synonymous	Exon 24 of 27	ENSP00000512341.1	A0A8Q3SIA1
	CFHR3	ENST00000471440.6	TSL:1	c.354C>T	p.Tyr118Tyr	synonymous	Exon 3 of 5	ENSP00000436258.1	Q6NSD3

Frequencies

GnomAD3 genomes AF: 0.000256 AC: 35 AN: 136628 Hom.: 6 Cov.: 25

Gnomad AFR AF: 0.0000920

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000706

Gnomad ASJ AF: 0.00878

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000465

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000566 AC: 135 AN: 238676 AF XY: 0.000552

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000411

Gnomad ASJ exome AF: 0.0113

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000826

Gnomad OTH exome AF: 0.00103

GnomAD4 exome AF: 0.000261 AC: 365 AN: 1396426 Hom.: 70 Cov.: 31 AF XY: 0.000265 AC XY: 184 AN XY: 693222

African (AFR) AF: 0.00 AC: 0 AN: 27838

American (AMR) AF: 0.000591 AC: 26 AN: 43996

Ashkenazi Jewish (ASJ) AF: 0.0104 AC: 253 AN: 24384

East Asian (EAS) AF: 0.00 AC: 0 AN: 39572

South Asian (SAS) AF: 0.00 AC: 0 AN: 76730

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52478

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5112

European-Non Finnish (NFE) AF: 0.0000458 AC: 49 AN: 1068888

Other (OTH) AF: 0.000644 AC: 37 AN: 57428

GnomAD4 genome AF: 0.000256 AC: 35 AN: 136628 Hom.: 6 Cov.: 25 AF XY: 0.000226 AC XY: 15 AN XY: 66386

African (AFR) AF: 0.0000920 AC: 3 AN: 32608

American (AMR) AF: 0.0000706 AC: 1 AN: 14170

Ashkenazi Jewish (ASJ) AF: 0.00878 AC: 28 AN: 3190

East Asian (EAS) AF: 0.00 AC: 0 AN: 5102

South Asian (SAS) AF: 0.00 AC: 0 AN: 3888

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10118

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 272

European-Non Finnish (NFE) AF: 0.0000465 AC: 3 AN: 64542

Other (OTH) AF: 0.00 AC: 0 AN: 1848

Alfa AF: 0.000272 Hom.: 3

ClinVar

ClinVar submissions

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	not provided (3)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	4.0
DANN	Benign	0.20
PhyloP100		-1.7
Mutation Taster		=100/0	polymorphism

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

Other links and lift over

dbSNP: rs144398879; hg19: chr1-196749027;