rs10170348

chr2-3626058-G-A

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_Strong BP6_Moderate BP7 BA1

The ENST00000236693.11(COLEC11):c.159G>A(p.Lys53=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.139 in 1,613,134 control chromosomes in the GnomAD database, including 17,696 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.11 (1276 hom., cov: 33)
  • Exomes 𝑓: 0.14 (16420 hom.)
• Consequence: COLEC11 ENST00000236693.11 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.502

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 -15 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BP6: Variant 2-3626058-G-A is Benign according to our data. Variant chr2-3626058-G-A is described in ClinVar as [Benign]. Clinvar id is 402556.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr2-3626058-G-A is described in Lovd as [Benign].
• BP7: Synonymous conserved (PhyloP=0.502 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.304 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
COLEC11	NM_024027.5	c.203-11475G>A		intron_variant		ENST00000349077.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
COLEC11	ENST00000349077.9	c.203-11475G>A		intron_variant		1	NM_024027.5	P1

Frequencies

GnomAD3 genomes AF: 0.111 AC: 16820 AN: 152202 Hom.: 1278 Cov.: 33

Gnomad AFR AF: 0.0380

Gnomad AMI AF: 0.339

Gnomad AMR AF: 0.0834

Gnomad ASJ AF: 0.0836

Gnomad EAS AF: 0.316

Gnomad SAS AF: 0.0614

Gnomad FIN AF: 0.111

Gnomad MID AF: 0.0728

Gnomad NFE AF: 0.147

Gnomad OTH AF: 0.105

GnomAD3 exomes AF: 0.126 AC: 31634 AN: 251476 Hom.: 2698 AF XY: 0.125 AC XY: 16939 AN XY: 135914

Gnomad AFR exome AF: 0.0332

Gnomad AMR exome AF: 0.0597

Gnomad ASJ exome AF: 0.0869

Gnomad EAS exome AF: 0.329

Gnomad SAS exome AF: 0.0608

Gnomad FIN exome AF: 0.124

Gnomad NFE exome AF: 0.148

Gnomad OTH exome AF: 0.125

GnomAD4 exome AF: 0.142 AC: 207952 AN: 1460814 Hom.: 16420 Cov.: 32 AF XY: 0.140 AC XY: 101492 AN XY: 726732

Gnomad4 AFR exome AF: 0.0313

Gnomad4 AMR exome AF: 0.0618

Gnomad4 ASJ exome AF: 0.0882

Gnomad4 EAS exome AF: 0.309

Gnomad4 SAS exome AF: 0.0591

Gnomad4 FIN exome AF: 0.130

Gnomad4 NFE exome AF: 0.152

Gnomad4 OTH exome AF: 0.139

GnomAD4 genome AF: 0.110 AC: 16819 AN: 152320 Hom.: 1276 Cov.: 33 AF XY: 0.108 AC XY: 8042 AN XY: 74476

Gnomad4 AFR AF: 0.0379

Gnomad4 AMR AF: 0.0833

Gnomad4 ASJ AF: 0.0836

Gnomad4 EAS AF: 0.316

Gnomad4 SAS AF: 0.0621

Gnomad4 FIN AF: 0.111

Gnomad4 NFE AF: 0.147

Gnomad4 OTH AF: 0.104

Alfa AF: 0.134 Hom.: 1649

Bravo AF: 0.108

Asia WGS AF: 0.145 AC: 504 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Mar 28, 2016

Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: Frequency -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
Cadd	Benign	1.3
Dann	Benign	0.41

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: rs10170348; hg19: chr2-3673648; COSMIC: COSV52595850;