Variant 1-196774952-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.58+8A>G variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000135 in 1,520,532 control chromosomes in the GnomAD database, including 6 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0013 ( 2 hom., cov: 25)

Exomes 𝑓: 0.000016 ( 4 hom. )

Consequence

CFHR3
NM_021023.6 splice_region, intron

Scores

Splicing: ADA: 0.00001400

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.677

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 -10 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.99).

BP6

Variant 1-196774952-A-G is Benign according to our data. Variant chr1-196774952-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 782688.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAd4 at 2 AD,AR,Digenic gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CFHR3	NM_021023.6 linkuse as main transcript	c.58+8A>G		splice_region_variant, intron_variant		ENST00000367425.9
CFHR3	NM_001166624.2 linkuse as main transcript	c.58+8A>G		splice_region_variant, intron_variant

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	MANE	Appris	UniProt
CFHR3	ENST00000367425.9 linkuse as main transcript	c.58+8A>G	splice_region_variant, intron_variant	1	NM_021023.6	P1	Q02985-1
CFHR3	ENST00000471440.6 linkuse as main transcript	c.58+8A>G	splice_region_variant, intron_variant	1
CFHR3	ENST00000391985.7 linkuse as main transcript	c.58+8A>G	splice_region_variant, intron_variant	2			Q02985-2
CFHR3	ENST00000367427.7 linkuse as main transcript	c.58+8A>G	splice_region_variant, intron_variant, NMD_transcript_variant	5

Frequencies

GnomAD3 genomes

AF:

0.00135

AC:

185

AN:

136896

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000273

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0121

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000194

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000310

Gnomad OTH

AF:

0.00217

GnomAD3 exomes

AF:

0.0000126

AC:

AN:

238120

Hom.:

AF XY:

0.0000156

AC XY:

AN XY:

128404

show subpopulations

Gnomad AFR exome

AF:

0.0000733

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:

0.00000919

Gnomad OTH exome

AF:

0.000172

GnomAD4 exome

AF:

0.0000159

AC:

AN:

1383514

Hom.:

Cov.:

AF XY:

0.0000175

AC XY:

AN XY:

687640

show subpopulations

Gnomad4 AFR exome

AF:

0.00

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:

0.0000161

Gnomad4 OTH exome

AF:

0.0000878

GnomAD4 genome

AF:

0.00134

AC:

184

AN:

137018

Hom.:

Cov.:

AF XY:

0.00148

AC XY:

AN XY:

66724

show subpopulations

Gnomad4 AFR

AF:

0.000272

Gnomad4 AMR

AF:

0.0120

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000195

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000310

Gnomad4 OTH

AF:

0.00215

Alfa

AF:

0.00135

Hom.:

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Dec 31, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.99

CADD

Benign

1.4

DANN

Benign

0.46

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000014

dbscSNV1_RF

Benign

0.0040

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