8-119102406-G-A

Variant names:

• chr8-119102406-G-A
• rs73327239
• NM_006438.5:c.346+5G>A

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_006438.5(COLEC10):​c.346+5G>A variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00485 in 1,605,140 control chromosomes in the GnomAD database, including 318 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.025 (156 hom., cov: 32)
  • Exomes 𝑓: 0.0027 (162 hom.)
• Consequence: COLEC10 NM_006438.5 splice_region, intron
• Scores: Splicing: ADA: 0.7391
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.0550
• Publications: 1 publications found

Genes affected

COLEC10 (HGNC:2220): (collectin subfamily member 10) This gene encodes a member of the C-lectin family, proteins that possess collagen-like sequences and carbohydrate recognition domains. The other members of this family are secreted proteins and bind to carbohydrate antigens on microorganisms facilitating their recognition and removal. This gene product is a cytosolic protein, a characteristic that suggests that it may have different biological functions than other C-lectins. [provided by RefSeq, Jul 2008]

COLEC10 Gene-Disease associations (from GenCC):

• 3MC syndrome 3

  Inheritance: AR Classification: STRONG Submitted by: G2P
• 3MC syndrome

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.74).
• BP6: Variant 8-119102406-G-A is Benign according to our data. Variant chr8-119102406-G-A is described in ClinVar as [Benign]. Clinvar id is 773765.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0854 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
COLEC10	NM_006438.5	c.346+5G>A		splice_region_variant, intron_variant	Intron 4 of 5	ENST00000332843.3	NP_006429.2
COLEC10	NM_001324095.2	c.139+5G>A		splice_region_variant, intron_variant	Intron 6 of 7		NP_001311024.1
COLEC10	XM_005250756.4	c.139+5G>A		splice_region_variant, intron_variant	Intron 4 of 5		XP_005250813.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
COLEC10	ENST00000332843.3	c.346+5G>A		splice_region_variant, intron_variant	Intron 4 of 5	1	NM_006438.5	ENSP00000332723.2
COLEC10	ENST00000521788.1	n.433+5G>A		splice_region_variant, intron_variant	Intron 5 of 6	3

Frequencies

GnomAD3 genomes AF: 0.0252 AC: 3829 AN: 151772 Hom.: 155 Cov.: 32

Gnomad AFR AF: 0.0874

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0110

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000624

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00949

Gnomad NFE AF: 0.000176

Gnomad OTH AF: 0.0196

GnomAD2 exomes AF: 0.00729 AC: 1809 AN: 248142 AF XY: 0.00562

Gnomad AFR exome AF: 0.0922

Gnomad AMR exome AF: 0.00760

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000553

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000169

Gnomad OTH exome AF: 0.00549

GnomAD4 exome AF: 0.00270 AC: 3927 AN: 1453250 Hom.: 162 Cov.: 29 AF XY: 0.00244 AC XY: 1764 AN XY: 722948

African (AFR) AF: 0.0903 AC: 2991 AN: 33112

American (AMR) AF: 0.00820 AC: 363 AN: 44256

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25976

East Asian (EAS) AF: 0.0000254 AC: 1 AN: 39412

South Asian (SAS) AF: 0.000306 AC: 26 AN: 84858

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53226

Middle Eastern (MID) AF: 0.00541 AC: 31 AN: 5726

European-Non Finnish (NFE) AF: 0.000132 AC: 146 AN: 1106648

Other (OTH) AF: 0.00615 AC: 369 AN: 60036

GnomAD4 genome AF: 0.0254 AC: 3852 AN: 151890 Hom.: 156 Cov.: 32 AF XY: 0.0241 AC XY: 1792 AN XY: 74238

African (AFR) AF: 0.0877 AC: 3628 AN: 41348

American (AMR) AF: 0.0110 AC: 168 AN: 15248

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 5172

South Asian (SAS) AF: 0.00 AC: 0 AN: 4802

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10552

Middle Eastern (MID) AF: 0.0102 AC: 3 AN: 294

European-Non Finnish (NFE) AF: 0.000177 AC: 12 AN: 67984

Other (OTH) AF: 0.0194 AC: 41 AN: 2110

Alfa AF: 0.0128 Hom.: 155

Bravo AF: 0.0288

Asia WGS AF: 0.00751 AC: 27 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Dec 31, 2019

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.74
CADD	Benign	8.9
DANN	Benign	0.56
PhyloP100		0.055
Mutation Taster		=96/4	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.74
dbscSNV1_RF	Benign	0.61
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: rs73327239; hg19: chr8-120114645; COSMIC: COSV60521990;