chr1-207683889-C-A

Position:

• chr1-207683889-C-A

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_175710.2(CR1L):​c.395C>A​(p.Ser132Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: CR1L NM_175710.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.683

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]

ACMG classification

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=0.369749).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CR1L	NM_175710.2	c.395C>A	p.Ser132Tyr	missense_variant	4/12	ENST00000508064.7	NP_783641.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CR1L	ENST00000508064.7	c.395C>A	p.Ser132Tyr	missense_variant	4/12	1	NM_175710.2	ENSP00000421736.2
CR1L	ENST00000294997.10	n.227C>A		non_coding_transcript_exon_variant	3/13	1		ENSP00000434864.1
CR1L	ENST00000530905.1	n.425C>A		non_coding_transcript_exon_variant	4/5	5
CR1L	ENST00000531844.5	n.516C>A		non_coding_transcript_exon_variant	4/4	2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Oct 12, 2021

The c.395C>A (p.S132Y) alteration is located in exon 4 (coding exon 4) of the CR1L gene. This alteration results from a C to A substitution at nucleotide position 395, causing the serine (S) at amino acid position 132 to be replaced by a tyrosine (Y). 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	0.15
BayesDel_addAF	Benign	-0.12	T
BayesDel_noAF	Benign	-0.40
CADD	Benign	11
DANN	Uncertain	0.98
DEOGEN2	Benign	0.057	T
Eigen	Benign	-0.25
Eigen_PC	Benign	-0.54
FATHMM_MKL	Benign	0.0026	N
LIST_S2	Benign	0.73	T
M_CAP	Benign	0.021	T
MetaRNN	Benign	0.37	T
MetaSVM	Benign	-0.53	T
MutationAssessor	Uncertain	2.8	M
PrimateAI	Benign	0.32	T
PROVEAN	Uncertain	-2.7	D
REVEL	Benign	0.23
Sift	Benign	0.051	T
Sift4G	Uncertain	0.031	D
Polyphen		0.83	P
Vest4		0.26
MutPred		0.60		Loss of disorder (P = 0.1621);
MVP		0.38
MPC		0.62
ClinPred		0.88	D
GERP RS		0.46
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.15
gMVP		0.21

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr1-207857234;