rs7567833

chr2-3643958-A-G

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_024027.5(COLEC11):c.656A>G(p.His219Arg) variant causes a missense change. The variant allele was found at a frequency of 0.0685 in 1,613,746 control chromosomes in the GnomAD database, including 19,382 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

• Frequency:
  • Genomes: 𝑓 0.22 (9520 hom., cov: 34)
  • Exomes 𝑓: 0.053 (9862 hom.)
• Consequence: COLEC11 NM_024027.5 missense
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 4.72

Genes affected

COLEC11 (HGNC:17213): (collectin subfamily member 11) This gene encodes a member of the collectin family of C-type lectins that possess collagen-like sequences and carbohydrate recognition domains. Collectins are secreted proteins that play important roles in the innate immune system by binding to carbohydrate antigens on microorganisms, facilitating their recognition and removal. The encoded protein binds to multiple sugars with a preference for fucose and mannose. Mutations in this gene are a cause of 3MC syndrome-2. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene. [provided by RefSeq, Dec 2011]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=7.5731377E-6).
• BP6: Variant 2-3643958-A-G is Benign according to our data. Variant chr2-3643958-A-G is described in ClinVar as [Benign]. Clinvar id is 1588878.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.661 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
COLEC11	NM_024027.5	c.656A>G	p.His219Arg	missense_variant	7/7	ENST00000349077.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
COLEC11	ENST00000349077.9	c.656A>G	p.His219Arg	missense_variant	7/7	1	NM_024027.5	P1

Frequencies

GnomAD3 genomes AF: 0.215 AC: 32710 AN: 151850 Hom.: 9482 Cov.: 34

Gnomad AFR AF: 0.667

Gnomad AMI AF: 0.0428

Gnomad AMR AF: 0.0922

Gnomad ASJ AF: 0.0386

Gnomad EAS AF: 0.0213

Gnomad SAS AF: 0.110

Gnomad FIN AF: 0.0167

Gnomad MID AF: 0.165

Gnomad NFE AF: 0.0336

Gnomad OTH AF: 0.188

GnomAD3 exomes AF: 0.0845 AC: 21235 AN: 251312 Hom.: 4159 AF XY: 0.0749 AC XY: 10176 AN XY: 135868

Gnomad AFR exome AF: 0.685

Gnomad AMR exome AF: 0.0485

Gnomad ASJ exome AF: 0.0367

Gnomad EAS exome AF: 0.0171

Gnomad SAS exome AF: 0.103

Gnomad FIN exome AF: 0.0186

Gnomad NFE exome AF: 0.0339

Gnomad OTH exome AF: 0.0592

GnomAD4 exome AF: 0.0531 AC: 77681 AN: 1461780 Hom.: 9862 Cov.: 32 AF XY: 0.0528 AC XY: 38427 AN XY: 727196

Gnomad4 AFR exome AF: 0.692

Gnomad4 AMR exome AF: 0.0540

Gnomad4 ASJ exome AF: 0.0375

Gnomad4 EAS exome AF: 0.0181

Gnomad4 SAS exome AF: 0.104

Gnomad4 FIN exome AF: 0.0193

Gnomad4 NFE exome AF: 0.0313

Gnomad4 OTH exome AF: 0.0811

GnomAD4 genome AF: 0.216 AC: 32804 AN: 151966 Hom.: 9520 Cov.: 34 AF XY: 0.210 AC XY: 15594 AN XY: 74258

Gnomad4 AFR AF: 0.667

Gnomad4 AMR AF: 0.0921

Gnomad4 ASJ AF: 0.0386

Gnomad4 EAS AF: 0.0214

Gnomad4 SAS AF: 0.110

Gnomad4 FIN AF: 0.0167

Gnomad4 NFE AF: 0.0336

Gnomad4 OTH AF: 0.187

Alfa AF: 0.0684 Hom.: 4170

Bravo AF: 0.239

TwinsUK AF: 0.0324 AC: 120

ALSPAC AF: 0.0304 AC: 117

ESP6500AA AF: 0.660 AC: 2910

ESP6500EA AF: 0.0324 AC: 279

ExAC AF: 0.0987 AC: 11983

Asia WGS AF: 0.107 AC: 376 AN: 3478

EpiCase AF: 0.0351

EpiControl AF: 0.0359

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jan 31, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.046
BayesDel_addAF	Benign	-0.72	T
BayesDel_noAF	Benign	-0.66
Cadd	Benign	16
Dann	Benign	0.83
Eigen	Benign	-0.68
Eigen_PC	Benign	-0.45
FATHMM_MKL	Benign	0.11	N
LIST_S2	Benign	0.34	T;T;T;T;T;T;T;T
MetaRNN	Benign	0.0000076	T;T;T;T;T;T;T;T
MetaSVM	Benign	-1.0	T
MutationTaster	Benign	1.0	P;P;P;P;P;P;P;P
PrimateAI	Uncertain	0.50	T
PROVEAN	Benign	0.13	N;N;N;N;N;N;N;N
REVEL	Benign	0.14
Sift	Benign	0.48	T;T;T;T;T;T;T;T
Sift4G	Benign	0.62	T;T;T;T;T;T;T;T
Polyphen		0.0	B;B;B;.;B;B;B;B
Vest4		0.11
MPC		0.47
ClinPred		0.0040	T
GERP RS		5.3
Varity_R		0.25
gMVP		0.54

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

LitVar

Other links and lift over

dbSNP: rs7567833; hg19: chr2-3691548; COSMIC: COSV52593465; COSMIC: COSV52593465;