1-207677404-C-T

Variant names:

• chr1-207677404-C-T
• rs751894755
• NM_175710.2:c.113C>T

Variant summary

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

The NM_175710.2(CR1L):​c.113C>T​(p.Pro38Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000701 in 1,611,232 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000092 (0 hom., cov: 31)
  • Exomes 𝑓: 0.000068 (0 hom.)
• Consequence: CR1L NM_175710.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.62
• Publications: 2 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 0 ACMG points.

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.113C>T	p.Pro38Leu	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.113C>T	p.Pro38Leu	missense	Exon 2 of 12	ENSP00000421736.2	Q2VPA4-1
	CR1L	ENST00000430248.5	TSL:3	n.117C>T		non_coding_transcript_exon	Exon 2 of 3
	CR1L	ENST00000530905.1	TSL:5	n.143C>T		non_coding_transcript_exon	Exon 2 of 5

Frequencies

GnomAD3 genomes AF: 0.0000924 AC: 14 AN: 151594 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.000218

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000589

Gnomad OTH AF: 0.000481

GnomAD2 exomes AF: 0.000105 AC: 26 AN: 247674 AF XY: 0.000104

Gnomad AFR exome AF: 0.000391

Gnomad AMR exome AF: 0.0000879

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000142

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000678 AC: 99 AN: 1459638 Hom.: 0 Cov.: 35 AF XY: 0.0000730 AC XY: 53 AN XY: 726030

African (AFR) AF: 0.000270 AC: 9 AN: 33394

American (AMR) AF: 0.000112 AC: 5 AN: 44590

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26086

East Asian (EAS) AF: 0.0000253 AC: 1 AN: 39590

South Asian (SAS) AF: 0.0000699 AC: 6 AN: 85844

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53314

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5760

European-Non Finnish (NFE) AF: 0.0000675 AC: 75 AN: 1110778

Other (OTH) AF: 0.0000498 AC: 3 AN: 60282

GnomAD4 genome AF: 0.0000924 AC: 14 AN: 151594 Hom.: 0 Cov.: 31 AF XY: 0.0000946 AC XY: 7 AN XY: 73970

African (AFR) AF: 0.000218 AC: 9 AN: 41226

American (AMR) AF: 0.00 AC: 0 AN: 15218

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5178

South Asian (SAS) AF: 0.00 AC: 0 AN: 4808

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10436

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 314

European-Non Finnish (NFE) AF: 0.0000589 AC: 4 AN: 67958

Other (OTH) AF: 0.000481 AC: 1 AN: 2080

Alfa AF: 0.000135 Hom.: 0

Bravo AF: 0.000181

ExAC AF: 0.000116 AC: 14

EpiCase AF: 0.000109

EpiControl AF: 0.000119

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.24
BayesDel_addAF	Benign	-0.18	T
BayesDel_noAF	Benign	-0.18
CADD	Benign	19
DANN	Benign	0.94
DEOGEN2	Benign	0.023	T
Eigen	Benign	-0.038
Eigen_PC	Benign	-0.31
FATHMM_MKL	Benign	0.047	N
LIST_S2	Benign	0.76	T
M_CAP	Uncertain	0.091	D
MetaRNN	Uncertain	0.72	D
MetaSVM	Uncertain	-0.14	T
MutationAssessor	Uncertain	2.8	M
PhyloP100		2.6
PrimateAI	Benign	0.35	T
PROVEAN	Pathogenic	-5.4	D
REVEL	Uncertain	0.36
Sift	Benign	0.69	T
Sift4G	Benign	0.98	T
Polyphen		1.0	D
Vest4		0.57
MVP		0.48
MPC		0.56
ClinPred		0.66	D
GERP RS		2.5
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.095
gMVP		0.91
Mutation Taster		=97/3	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.090		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: rs751894755; hg19: chr1-207850749; COSMIC: COSV99687235; COSMIC: COSV99687235;