Variant 1-196774896-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_StrongBP6_ModerateBP7BS1BS2

The NM_021023.6(CFHR3):c.10C>T(p.Leu4=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00197 in 1,528,294 control chromosomes in the GnomAD database, including 805 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.010 ( 365 hom., cov: 25)

Exomes 𝑓: 0.0012 ( 440 hom. )

Consequence

CFHR3
NM_021023.6 synonymous

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.118

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 -15 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.89).

BP6

Variant 1-196774896-C-T is Benign according to our data. Variant chr1-196774896-C-T is described in ClinVar as [Benign]. Clinvar id is 775632.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr1-196774896-C-T is described in Lovd as [Likely_benign].

BP7

Synonymous conserved (PhyloP=0.118 with no splicing effect.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0101 (1390/137174) while in subpopulation AFR AF= 0.0395 (1308/33100). AF 95% confidence interval is 0.0377. There are 365 homozygotes in gnomad4. There are 691 alleles in male gnomad4 subpopulation. Median coverage is 25. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 365 AD,AR,Digenic gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CFHR3	NM_021023.6 linkuse as main transcript	c.10C>T	p.Leu4=	synonymous_variant	1/6	ENST00000367425.9
CFHR3	NM_001166624.2 linkuse as main transcript	c.10C>T	p.Leu4=	synonymous_variant	1/5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CFHR3	ENST00000367425.9 linkuse as main transcript	c.10C>T	p.Leu4=	synonymous_variant	1/6	1	NM_021023.6	P1	Q02985-1
CFHR3	ENST00000471440.6 linkuse as main transcript	c.10C>T	p.Leu4=	synonymous_variant	1/5	1
CFHR3	ENST00000391985.7 linkuse as main transcript	c.10C>T	p.Leu4=	synonymous_variant	1/5	2			Q02985-2
CFHR3	ENST00000367427.7 linkuse as main transcript	c.10C>T	p.Leu4=	synonymous_variant, NMD_transcript_variant	1/7	5

Frequencies

GnomAD3 genomes

AF:

0.0101

AC:

1382

AN:

137050

Hom.:

363

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0394

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00462

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00370

Gnomad NFE

AF:

0.000124

Gnomad OTH

AF:

0.00437

GnomAD3 exomes

AF:

0.00275

AC:

656

AN:

238280

Hom.:

182

AF XY:

0.00215

AC XY:

276

AN XY:

128470

show subpopulations

Gnomad AFR exome

AF:

0.0431

Gnomad AMR exome

AF:

0.00127

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000110

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000129

Gnomad OTH exome

AF:

0.00137

GnomAD4 exome

AF:

0.00117

AC:

1628

AN:

1391120

Hom.:

440

Cov.:

AF XY:

0.00107

AC XY:

737

AN XY:

690882

show subpopulations

Gnomad4 AFR exome

AF:

0.0435

Gnomad4 AMR exome

AF:

0.00183

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000914

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000142

Gnomad4 OTH exome

AF:

0.00276

GnomAD4 genome

AF:

0.0101

AC:

1390

AN:

137174

Hom.:

365

Cov.:

AF XY:

0.0103

AC XY:

691

AN XY:

66816

show subpopulations

Gnomad4 AFR

AF:

0.0395

Gnomad4 AMR

AF:

0.00461

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000124

Gnomad4 OTH

AF:

0.00432

Alfa

AF:

0.00351

Hom.:

Asia WGS

AF:

0.00433

AC:

AN:

3250

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

Invitae

Dec 31, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.89

CADD

Benign

3.7

DANN

Benign

0.48

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