Variant chr1-196779897-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -17 ACMG points: 0P and 17B. BP4_StrongBP6_Very_StrongBP7BS2

The NM_021023.6(CFHR3):c.354C>T(p.Tyr118=) 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

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -1.67

Variant links:

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 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -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 [Likely_benign]. Clinvar id 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 AD,AR,Digenic gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CFHR3	NM_021023.6 linkuse as main transcript	c.354C>T	p.Tyr118=	synonymous_variant	3/6	ENST00000367425.9
CFHR3	NM_001166624.2 linkuse as main transcript	c.354C>T	p.Tyr118=	synonymous_variant	3/5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CFHR3	ENST00000367425.9 linkuse as main transcript	c.354C>T	p.Tyr118=	synonymous_variant	3/6	1	NM_021023.6	P1	Q02985-1
CFHR3	ENST00000471440.6 linkuse as main transcript	c.354C>T	p.Tyr118=	synonymous_variant	3/5	1
CFHR3	ENST00000391985.7 linkuse as main transcript	c.354C>T	p.Tyr118=	synonymous_variant	3/5	2			Q02985-2
CFHR3	ENST00000367427.7 linkuse as main transcript	c.354C>T	p.Tyr118=	synonymous_variant, NMD_transcript_variant	3/7	5

Frequencies

GnomAD3 genomes

AF:

0.000256

AC:

AN:

136628

Hom.:

Cov.:

show subpopulations

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

GnomAD3 exomes

AF:

0.000566

AC:

135

AN:

238676

Hom.:

AF XY:

0.000552

AC XY:

AN XY:

128648

show subpopulations

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 SAS 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.:

Cov.:

AF XY:

0.000265

AC XY:

184

AN XY:

693222

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.000591

Gnomad4 ASJ exome

AF:

0.0104

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000458

Gnomad4 OTH exome

AF:

0.000644

GnomAD4 genome

AF:

0.000256

AC:

AN:

136628

Hom.:

Cov.:

AF XY:

0.000226

AC XY:

AN XY:

66386

show subpopulations

Gnomad4 AFR

AF:

0.0000920

Gnomad4 AMR

AF:

0.0000706

Gnomad4 ASJ

AF:

0.00878

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000465

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000389

Hom.:

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Likely benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Nov 01, 2023	CFHR3: BP4, BP7, BS2; ENSG00000289697: BS2 -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jul 21, 2018	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.90

CADD

Benign

4.0

DANN

Benign

0.20

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over