Variant chr1-207677533-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_175710.2(CR1L):c.242A>G(p.Asn81Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000479 in 1,461,666 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 31)

Exomes 𝑓: 0.0000048 ( 0 hom. )

Consequence

CR1L
NM_175710.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.545

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]

CR1L links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.31965858).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CR1L	NM_175710.2 link	c.242A>G	p.Asn81Ser	missense_variant	2/12	ENST00000508064.7	NP_783641.1	Q2VPA4-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CR1L	ENST00000508064.7 link	c.242A>G	p.Asn81Ser	missense_variant	2/12	1	NM_175710.2	ENSP00000421736.2		Q2VPA4-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000803

AC:

AN:

249184

Hom.:

AF XY:

0.00000740

AC XY:

AN XY:

135186

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:

0.00000885

Gnomad OTH exome

AF:

0.000165

GnomAD4 exome

AF:

0.00000479

AC:

AN:

1461666

Hom.:

Cov.:

AF XY:

0.00000550

AC XY:

AN XY:

727118

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:

0.00000540

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

Cov.:

Alfa

AF:

0.0000312

Hom.:

ExAC

AF:

0.00000828

AC:

EpiCase

AF:

0.00

EpiControl

AF:

0.0000593

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jun 22, 2023

The c.242A>G (p.N81S) alteration is located in exon 2 (coding exon 2) of the CR1L gene. This alteration results from a A to G substitution at nucleotide position 242, causing the asparagine (N) at amino acid position 81 to be replaced by a serine (S). 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

Benign

0.14

BayesDel_addAF

Benign

-0.23

BayesDel_noAF

Benign

-0.55

CADD

Benign

2.5

DANN

Benign

0.94

DEOGEN2

Benign

0.0039

Eigen

Benign

-0.37

Eigen_PC

Benign

-0.64

FATHMM_MKL

Benign

0.036

LIST_S2

Benign

0.76

M_CAP

Benign

0.019

MetaRNN

Benign

0.32

MetaSVM

Benign

-0.74

MutationAssessor

Uncertain

2.5

PrimateAI

Benign

0.41

PROVEAN

Benign

-2.4

REVEL

Benign

0.16

Sift

Benign

0.13

Sift4G

Uncertain

0.029

Polyphen

0.89

Vest4

0.24

MutPred

0.68

Gain of disorder (P = 0.0628);

MVP

0.19

MPC

0.23

ClinPred

0.16

GERP RS

1.3

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.043

gMVP

0.34

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