chr1-207677461-T-A

Variant names:

• chr1-207677461-T-A
• rs377607560
• NM_175710.2:c.170T>A

Variant summary

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

The NM_175710.2(CR1L):​c.170T>A​(p.Ile57Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,668 control chromosomes in the GnomAD database, with no homozygous occurrence. 13/22 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. I57F) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: CR1L NM_175710.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.733
• Publications: 0 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: 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.170T>A	p.Ile57Asn	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.170T>A	p.Ile57Asn	missense	Exon 2 of 12	ENSP00000421736.2	Q2VPA4-1
	CR1L	ENST00000294997.10	TSL:1	n.2T>A		non_coding_transcript_exon	Exon 1 of 13	ENSP00000434864.1	A0A0C4DGF5
	CR1L	ENST00000430248.5	TSL:3	n.174T>A		non_coding_transcript_exon	Exon 2 of 3

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461668 Hom.: 0 Cov.: 35 AF XY: 0.00 AC XY: 0 AN XY: 727110

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

American (AMR) AF: 0.00 AC: 0 AN: 44716

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

East Asian (EAS) AF: 0.0000252 AC: 1 AN: 39696

South Asian (SAS) AF: 0.00 AC: 0 AN: 86244

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53402

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1111860

Other (OTH) AF: 0.00 AC: 0 AN: 60368

GnomAD4 genome Cov.: 31

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000113

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.21
BayesDel_addAF	Benign	-0.069	T
BayesDel_noAF	Benign	-0.34
CADD	Benign	17
DANN	Uncertain	0.99
DEOGEN2	Benign	0.028	T
Eigen	Benign	-0.027
Eigen_PC	Benign	-0.19
FATHMM_MKL	Benign	0.29	N
LIST_S2	Benign	0.80	T
M_CAP	Benign	0.036	D
MetaRNN	Uncertain	0.50	T
MetaSVM	Benign	-0.79	T
MutationAssessor	Uncertain	2.3	M
PhyloP100		0.73
PrimateAI	Benign	0.35	T
PROVEAN	Pathogenic	-4.8	D
REVEL	Benign	0.21
Sift	Uncertain	0.0010	D
Sift4G	Pathogenic	0.0010	D
Polyphen		0.94	P
Vest4		0.40
MutPred		0.63		Gain of disorder (P = 0.0553)
MVP		0.43
MPC		0.69
ClinPred		0.99	D
GERP RS		2.5
Varity_R		0.44
gMVP		0.74
Mutation Taster		=95/5	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs377607560; hg19: chr1-207850806;