Variant 1-196779842-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_021023.6(CFHR3):c.299A>G(p.Tyr100Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000461 in 1,532,386 control chromosomes in the GnomAD database, including 187 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0027 ( 100 hom., cov: 26)

Exomes 𝑓: 0.00024 ( 87 hom. )

Consequence

CFHR3
NM_021023.6 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -4.67

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.008261234).

BP6

Variant 1-196779842-A-G is Benign according to our data. Variant chr1-196779842-A-G is described in ClinVar as [Benign]. Clinvar id is 767739.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAd4 at 100 AD,AR,Digenic gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CFHR3	NM_021023.6 linkuse as main transcript	c.299A>G	p.Tyr100Cys	missense_variant	3/6	ENST00000367425.9	NP_066303.2
CFHR3	NM_001166624.2 linkuse as main transcript	c.299A>G	p.Tyr100Cys	missense_variant	3/5		NP_001160096.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CFHR3	ENST00000367425.9 linkuse as main transcript	c.299A>G	p.Tyr100Cys	missense_variant	3/6	1	NM_021023.6	ENSP00000356395	P1	Q02985-1
CFHR3	ENST00000471440.6 linkuse as main transcript	c.299A>G	p.Tyr100Cys	missense_variant	3/5	1		ENSP00000436258
CFHR3	ENST00000391985.7 linkuse as main transcript	c.299A>G	p.Tyr100Cys	missense_variant	3/5	2		ENSP00000375845		Q02985-2
CFHR3	ENST00000367427.7 linkuse as main transcript	c.299A>G	p.Tyr100Cys	missense_variant, NMD_transcript_variant	3/7	5		ENSP00000356397

Frequencies

GnomAD3 genomes

AF:

0.00273

AC:

374

AN:

137228

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0110

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000563

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00322

GnomAD3 exomes

AF:

0.000740

AC:

175

AN:

236494

Hom.:

AF XY:

0.000439

AC XY:

AN XY:

127448

show subpopulations

Gnomad AFR exome

AF:

0.0124

Gnomad AMR exome

AF:

0.000265

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000236

AC:

329

AN:

1395034

Hom.:

Cov.:

AF XY:

0.000194

AC XY:

134

AN XY:

692328

show subpopulations

Gnomad4 AFR exome

AF:

0.0103

Gnomad4 AMR exome

AF:

0.000273

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.000505

GnomAD4 genome

AF:

0.00274

AC:

377

AN:

137352

Hom.:

100

Cov.:

AF XY:

0.00263

AC XY:

176

AN XY:

66850

show subpopulations

Gnomad4 AFR

AF:

0.0110

Gnomad4 AMR

AF:

0.000562

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00318

Alfa

AF:

0.00122

Hom.:

ESP6500AA

AF:

0.0113

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.000910

AC:

105

Asia WGS

AF:

0.000616

AC:

AN:

3258

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Oct 10, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.36

BayesDel_addAF

Benign

-0.38

BayesDel_noAF

Benign

-0.49

CADD

Benign

0.0010

DANN

Benign

0.90

DEOGEN2

Benign

0.052

T;T;.;T

Eigen

Benign

-1.2

Eigen_PC

Benign

-1.5

FATHMM_MKL

Benign

0.0020

LIST_S2

Benign

0.68

T;.;T;T

MetaRNN

Benign

0.0083

T;T;T;T

MetaSVM

Benign

-0.82

MutationAssessor

Uncertain

2.1

M;.;M;.

MutationTaster

Benign

1.0

N;N;N

PrimateAI

Benign

0.34

PROVEAN

Uncertain

-2.5

N;D;N;.

REVEL

Benign

0.26

Sift

Benign

0.18

T;T;T;.

Sift4G

Benign

0.15

T;T;T;T

Polyphen

0.95

P;P;.;.

Vest4

0.16

MVP

0.30

MPC

0.20

ClinPred

0.085

GERP RS

-7.1

Varity_R

0.048

gMVP

0.49

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