NM_021023.6:c.99_105delATTTCAT

Variant summary

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

The NM_021023.6(CFHR3):​c.99_105delATTTCAT​(p.Phe34ArgfsTer10) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000974 in 1,530,002 control chromosomes in the GnomAD database, including 29 homozygotes. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000044 ( 1 hom., cov: 25)
Exomes 𝑓: 0.00010 ( 28 hom. )

Consequence

CFHR3
NM_021023.6 frameshift

Scores

Not classified

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.90
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]

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 GnomAdExome4 at 28 AD,AR,Digenic gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
CFHR3NM_021023.6 linkc.99_105delATTTCAT p.Phe34ArgfsTer10 frameshift_variant Exon 2 of 6 ENST00000367425.9 NP_066303.2 Q02985-1
CFHR3NM_001166624.2 linkc.99_105delATTTCAT p.Phe34ArgfsTer10 frameshift_variant Exon 2 of 5 NP_001160096.1 Q02985-2

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
CFHR3ENST00000367425.9 linkc.99_105delATTTCAT p.Phe34ArgfsTer10 frameshift_variant Exon 2 of 6 1 NM_021023.6 ENSP00000356395.5 Q02985-1
ENSG00000289697ENST00000696032.1 linkc.3621_3627delATTTCAT p.Phe1208ArgfsTer10 frameshift_variant Exon 23 of 27 ENSP00000512341.1 A0A8Q3SIA1

Frequencies

GnomAD3 genomes
AF:
0.0000438
AC:
6
AN:
136962
Hom.:
1
Cov.:
25
show subpopulations
Gnomad AFR
AF:
0.00
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:
0.0000929
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000252
AC:
6
AN:
238034
Hom.:
1
AF XY:
0.0000312
AC XY:
4
AN XY:
128362
show subpopulations
Gnomad AFR exome
AF:
0.00
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:
0.0000554
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.000103
AC:
143
AN:
1393040
Hom.:
28
AF XY:
0.0000925
AC XY:
64
AN XY:
691796
show subpopulations
Gnomad4 AFR exome
AF:
0.0000361
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:
0.000129
Gnomad4 OTH exome
AF:
0.0000873
GnomAD4 genome
AF:
0.0000438
AC:
6
AN:
136962
Hom.:
1
Cov.:
25
AF XY:
0.0000451
AC XY:
3
AN XY:
66564
show subpopulations
Gnomad4 AFR
AF:
0.00
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:
0.0000929
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.000169
Hom.:
0
Bravo
AF:
0.0000491

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

Age related macular degeneration 1;C2749604:Hemolytic uremic syndrome, atypical, susceptibility to, 1 Uncertain:1
Sep 26, 2022
Department of Pathology and Laboratory Medicine, Sinai Health System
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: research

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Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction

Splicing

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.

Other links and lift over

dbSNP: rs770559507; hg19: chr1-196748330; API