chr8-119089747-G-A

Variant names:

• chr8-119089747-G-A
• rs116835812
• NM_006438.5:c.216G>A

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BS1 BS2

The NM_006438.5(COLEC10):​c.216G>A​(p.Pro72Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00114 in 1,612,090 control chromosomes in the GnomAD database, including 17 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0060 (9 hom., cov: 33)
  • Exomes 𝑓: 0.00063 (8 hom.)
• Consequence: COLEC10 NM_006438.5 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -3.92
• Publications: 2 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 -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BP6: Variant 8-119089747-G-A is Benign according to our data. Variant chr8-119089747-G-A is described in ClinVar as [Benign]. Clinvar id is 783530.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-3.92 with no splicing effect.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00603 (919/152298) while in subpopulation AFR AF = 0.0213 (885/41570). AF 95% confidence interval is 0.0201. There are 9 homozygotes in GnomAd4. There are 416 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 9 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
COLEC10	NM_006438.5	c.216G>A	p.Pro72Pro	synonymous_variant	Exon 2 of 6	ENST00000332843.3	NP_006429.2
COLEC10	NM_001324095.2	c.9G>A	p.Pro3Pro	synonymous_variant	Exon 4 of 8		NP_001311024.1
COLEC10	XM_005250756.4	c.9G>A	p.Pro3Pro	synonymous_variant	Exon 2 of 6		XP_005250813.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
COLEC10	ENST00000332843.3	c.216G>A	p.Pro72Pro	synonymous_variant	Exon 2 of 6	1	NM_006438.5	ENSP00000332723.2
COLEC10	ENST00000521788.1	n.303G>A		non_coding_transcript_exon_variant	Exon 3 of 7	3

Frequencies

GnomAD3 genomes AF: 0.00603 AC: 918 AN: 152180 Hom.: 9 Cov.: 33

Gnomad AFR AF: 0.0213

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00144

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: 0.0000735

Gnomad OTH AF: 0.00335

GnomAD2 exomes AF: 0.00156 AC: 392 AN: 250592 AF XY: 0.00126

Gnomad AFR exome AF: 0.0217

Gnomad AMR exome AF: 0.000696

Gnomad ASJ exome AF: 0.0000994

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000530

Gnomad OTH exome AF: 0.000820

GnomAD4 exome AF: 0.000627 AC: 915 AN: 1459792 Hom.: 8 Cov.: 29 AF XY: 0.000529 AC XY: 384 AN XY: 726274

African (AFR) AF: 0.0235 AC: 784 AN: 33422

American (AMR) AF: 0.000806 AC: 36 AN: 44684

Ashkenazi Jewish (ASJ) AF: 0.0000383 AC: 1 AN: 26126

East Asian (EAS) AF: 0.00 AC: 0 AN: 39622

South Asian (SAS) AF: 0.0000696 AC: 6 AN: 86192

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53354

Middle Eastern (MID) AF: 0.000347 AC: 2 AN: 5760

European-Non Finnish (NFE) AF: 0.0000207 AC: 23 AN: 1110350

Other (OTH) AF: 0.00105 AC: 63 AN: 60282

GnomAD4 genome AF: 0.00603 AC: 919 AN: 152298 Hom.: 9 Cov.: 33 AF XY: 0.00559 AC XY: 416 AN XY: 74462

African (AFR) AF: 0.0213 AC: 885 AN: 41570

American (AMR) AF: 0.00144 AC: 22 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5182

South Asian (SAS) AF: 0.00 AC: 0 AN: 4826

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10620

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0000735 AC: 5 AN: 68022

Other (OTH) AF: 0.00331 AC: 7 AN: 2114

Alfa AF: 0.00226 Hom.: 2

Bravo AF: 0.00691

Asia WGS AF: 0.000866 AC: 3 AN: 3478

EpiCase AF: 0.000164

EpiControl AF: 0.0000594

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	-0.92
CADD	Benign	0.086
DANN	Benign	0.37
PhyloP100		-3.9
Mutation Taster		=100/0	polymorphism

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

Other links and lift over

dbSNP: rs116835812; hg19: chr8-120101986; COSMIC: COSV60521453;