NM_175710.2:c.31T>C

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_175710.2(CR1L):​c.31T>C​(p.Phe11Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000192 in 1,613,614 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000021 ( 0 hom. )

Consequence

CR1L
NM_175710.2 missense

Scores

1
18

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -3.02
Variant links:
Genes affected
CR1L (HGNC:2335): (complement C3b/C4b receptor 1 like) Acts upstream of or within regulation of complement activation and regulation of complement-dependent cytotoxicity. Part of receptor complex. [provided by Alliance of Genome Resources, Apr 2022]
CD46P1 (HGNC:6959): (CD46 molecule pseudogene 1)

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.058642358).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
CR1LNM_175710.2 linkc.31T>C p.Phe11Leu missense_variant Exon 1 of 12 ENST00000508064.7 NP_783641.1 Q2VPA4-1
CD46P1 n.207645264T>C intragenic_variant

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
CR1LENST00000508064.7 linkc.31T>C p.Phe11Leu missense_variant Exon 1 of 12 1 NM_175710.2 ENSP00000421736.2 Q2VPA4-1
CD46P1ENST00000441364.1 linkn.31T>C non_coding_transcript_exon_variant Exon 1 of 5 6
CR1LENST00000531844.5 linkn.152T>C non_coding_transcript_exon_variant Exon 1 of 4 2

Frequencies

GnomAD3 genomes
AF:
0.00000657
AC:
1
AN:
152250
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0000241
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
GnomAD4 exome
AF:
0.0000205
AC:
30
AN:
1461364
Hom.:
0
Cov.:
31
AF XY:
0.0000206
AC XY:
15
AN XY:
726984
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:
0.0000261
Gnomad4 OTH exome
AF:
0.0000166
GnomAD4 genome
AF:
0.00000657
AC:
1
AN:
152250
Hom.:
0
Cov.:
32
AF XY:
0.0000134
AC XY:
1
AN XY:
74396
show subpopulations
Gnomad4 AFR
AF:
0.0000241
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
Bravo
AF:
0.00000378
ExAC
AF:
0.00000824
AC:
1
EpiCase
AF:
0.0000545
EpiControl
AF:
0.00

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
Apr 07, 2023
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.31T>C (p.F11L) alteration is located in exon 1 (coding exon 1) of the CR1L gene. This alteration results from a T to C substitution at nucleotide position 31, causing the phenylalanine (F) at amino acid position 11 to be replaced by a leucine (L). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Uncertain
0.41
BayesDel_addAF
Benign
-0.36
T
BayesDel_noAF
Benign
-0.75
CADD
Benign
0.16
DANN
Benign
0.71
DEOGEN2
Benign
0.0038
T
Eigen
Benign
-1.4
Eigen_PC
Benign
-1.5
FATHMM_MKL
Benign
0.035
N
LIST_S2
Benign
0.33
T
M_CAP
Benign
0.0019
T
MetaRNN
Benign
0.059
T
MetaSVM
Benign
-0.97
T
MutationAssessor
Benign
1.4
L
PrimateAI
Benign
0.37
T
PROVEAN
Benign
0.11
N
REVEL
Benign
0.0090
Sift
Benign
0.042
D
Sift4G
Benign
0.37
T
Polyphen
0.0020
B
Vest4
0.10
MutPred
0.18
Gain of loop (P = 0.1081);
MVP
0.030
MPC
0.16
ClinPred
0.066
T
GERP RS
-5.4
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.1
Varity_R
0.047
gMVP
0.61

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.

Other links and lift over

dbSNP: rs776195846; hg19: chr1-207818609; API