1-207694356-T-C

Variant names:

• chr1-207694356-T-C
• rs769932758
• NM_175710.2:c.467T>C

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_175710.2(CR1L):​c.467T>C​(p.Ile156Thr) variant causes a missense change. The variant allele was found at a frequency of 0.000000684 in 1,461,666 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. I156N) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: CR1L NM_175710.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.67
• Publications: 1 publications found

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]

ENSG00000308069 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_175710.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CR1L	NM_175710.2	MANE Select	c.467T>C	p.Ile156Thr	missense	Exon 5 of 12	NP_783641.1	Q2VPA4-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CR1L	ENST00000508064.7	TSL:1 MANE Select	c.467T>C	p.Ile156Thr	missense	Exon 5 of 12	ENSP00000421736.2	Q2VPA4-1
	CR1L	ENST00000294997.10	TSL:1	n.299T>C		non_coding_transcript_exon	Exon 4 of 13	ENSP00000434864.1	A0A0C4DGF5
	CR1L	ENST00000530905.1	TSL:5	n.493+10399T>C		intron	N/A

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD2 exomes AF: 0.00000402 AC: 1 AN: 249058 AF XY: 0.00000740

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 FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000886

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461666 Hom.: 0 Cov.: 32 AF XY: 0.00000138 AC XY: 1 AN XY: 727106

African (AFR) AF: 0.00 AC: 0 AN: 33478

American (AMR) AF: 0.00 AC: 0 AN: 44710

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39696

South Asian (SAS) AF: 0.00 AC: 0 AN: 86256

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53400

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5766

European-Non Finnish (NFE) AF: 8.99e-7 AC: 1 AN: 1111852

Other (OTH) AF: 0.00 AC: 0 AN: 60372

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.73
BayesDel_addAF	Benign	-0.067	T
BayesDel_noAF	Benign	-0.33
CADD	Benign	21
DANN	Uncertain	0.99
DEOGEN2	Benign	0.040	T
Eigen	Benign	0.086
Eigen_PC	Benign	-0.20
FATHMM_MKL	Benign	0.36	N
LIST_S2	Uncertain	0.88	D
M_CAP	Benign	0.0045	T
MetaRNN	Uncertain	0.56	D
MetaSVM	Benign	-1.0	T
MutationAssessor	Pathogenic	2.9	M
PhyloP100		3.7
PrimateAI	Uncertain	0.62	T
PROVEAN	Pathogenic	-4.7	D
REVEL	Benign	0.096
Sift	Pathogenic	0.0	D
Sift4G	Uncertain	0.0020	D
Polyphen		1.0	D
Vest4		0.56
MutPred		0.51		Loss of stability (P = 0.0021)
MVP		0.25
MPC		0.70
ClinPred		0.89	D
GERP RS		1.9
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.4
Varity_R		0.33
gMVP		0.17
Mutation Taster		=96/4	polymorphism

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

Other links and lift over

dbSNP: rs769932758; hg19: chr1-207867701;