Variant chr1-196779260-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS2

The NM_021023.6(CFHR3):c.157T>C(p.Tyr53His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000131 in 1,526,230 control chromosomes in the GnomAD database, including 6 homozygotes. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000080 ( 3 hom., cov: 25)

Exomes 𝑓: 0.0000065 ( 3 hom. )

Consequence

CFHR3
NM_021023.6 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.23

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 Likely_benign. Variant got -4 ACMG points.

BS2

High Homozygotes in GnomAd4 at 3 AD,AR,Digenic gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CFHR3	NM_021023.6 linkuse as main transcript	c.157T>C	p.Tyr53His	missense_variant	2/6	ENST00000367425.9
CFHR3	NM_001166624.2 linkuse as main transcript	c.157T>C	p.Tyr53His	missense_variant	2/5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CFHR3	ENST00000367425.9 linkuse as main transcript	c.157T>C	p.Tyr53His	missense_variant	2/6	1	NM_021023.6	P1	Q02985-1
CFHR3	ENST00000471440.6 linkuse as main transcript	c.157T>C	p.Tyr53His	missense_variant	2/5	1
CFHR3	ENST00000391985.7 linkuse as main transcript	c.157T>C	p.Tyr53His	missense_variant	2/5	2			Q02985-2
CFHR3	ENST00000367427.7 linkuse as main transcript	c.157T>C	p.Tyr53His	missense_variant, NMD_transcript_variant	2/7	5

Frequencies

GnomAD3 genomes

AF:

0.0000801

AC:

AN:

137362

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000334

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

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:

0.00

GnomAD3 exomes

AF:

0.0000210

AC:

AN:

238514

Hom.:

AF XY:

0.0000311

AC XY:

AN XY:

128576

show subpopulations

Gnomad AFR exome

AF:

0.000366

Gnomad AMR exome

AF:

0.00

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:

0.00000648

AC:

AN:

1388868

Hom.:

Cov.:

AF XY:

0.00000435

AC XY:

AN XY:

689956

show subpopulations

Gnomad4 AFR exome

AF:

0.000290

Gnomad4 AMR exome

AF:

0.00

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:

0.0000175

GnomAD4 genome

AF:

0.0000801

AC:

AN:

137362

Hom.:

Cov.:

AF XY:

0.0000898

AC XY:

AN XY:

66838

show subpopulations

Gnomad4 AFR

AF:

0.000334

Gnomad4 AMR

AF:

0.00

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:

0.00

ExAC

AF:

0.0000345

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Mayo Clinic Laboratories, Mayo Clinic

Nov 15, 2022

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.90

BayesDel_addAF

Uncertain

0.13

BayesDel_noAF

Uncertain

-0.060

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.40

T;T;.;T

Eigen

Benign

0.059

Eigen_PC

Benign

-0.22

FATHMM_MKL

Benign

0.15

LIST_S2

Uncertain

0.90

D;.;D;D

M_CAP

Benign

0.042

MetaRNN

Uncertain

0.44

T;T;T;T

MetaSVM

Benign

-0.44

MutationAssessor

Pathogenic

3.3

M;.;M;.

MutationTaster

Benign

1.0

N;N;N

PrimateAI

Uncertain

0.53

PROVEAN

Pathogenic

-4.9

D;D;D;.

REVEL

Uncertain

0.41

Sift

Pathogenic

0.0

D;D;D;.

Sift4G

Pathogenic

0.0

D;D;D;D

Polyphen

1.0

D;D;.;.

Vest4

0.57

MVP

0.71

MPC

0.55

ClinPred

0.52

GERP RS

2.9

Varity_R

0.47

gMVP

0.92

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