NM_175710.2:c.218C>A

Variant names:

• chr1-207677509-C-A
• rs750728001
• NM_175710.2:c.218C>A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_175710.2(CR1L):​c.218C>A​(p.Pro73Gln) 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. 17/22 in silico tools predict a benign outcome for this variant. 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. P73L) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 31)
• Consequence: CR1L NM_175710.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -6.00
• 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]

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.048853695).

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.218C>A	p.Pro73Gln	missense	Exon 2 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.218C>A	p.Pro73Gln	missense	Exon 2 of 12	ENSP00000421736.2	Q2VPA4-1
	CR1L	ENST00000294997.10	TSL:1	n.50C>A		non_coding_transcript_exon	Exon 1 of 13	ENSP00000434864.1	A0A0C4DGF5
	CR1L	ENST00000430248.5	TSL:3	n.222C>A		non_coding_transcript_exon	Exon 2 of 3

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD2 exomes AF: 0.00000401 AC: 1 AN: 249222 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: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome Cov.: 35

GnomAD4 genome Cov.: 31

ExAC AF: 0.00000828 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_addAF	Benign	-0.31	T
BayesDel_noAF	Benign	-0.58
CADD	Benign	0.0020
DANN	Benign	0.15
DEOGEN2	Benign	0.0018	T
Eigen	Benign	-1.5
Eigen_PC	Benign	-1.7
FATHMM_MKL	Benign	0.0012	N
LIST_S2	Benign	0.21	T
M_CAP	Benign	0.035	D
MetaRNN	Benign	0.049	T
MetaSVM	Benign	-0.97	T
MutationAssessor	Benign	1.2	L
PhyloP100		-6.0
PrimateAI	Benign	0.25	T
PROVEAN	Benign	0.16	N
REVEL	Benign	0.14
Sift	Benign	0.54	T
Sift4G	Benign	0.36	T
Polyphen		0.35	B
Vest4		0.20
MutPred		0.60		Gain of MoRF binding (P = 0.0606)
MVP		0.040
MPC		0.17
ClinPred		0.069	T
GERP RS		-5.1
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.022
gMVP		0.56
Mutation Taster		=100/0	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: rs750728001; hg19: chr1-207850854;