8-119102406-G-A

Variant summary

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

The NM_006438.5(COLEC10):c.346+5G>A variant causes a splice donor 5th base, 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_donor_5th_base, intron
• Scores: Splicing: ADA: 0.7391
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.0550

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]

ACMG classification

Verdict is Benign. Variant got -14 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_single_submitter, 1 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/exons	MANE	UniProt
COLEC10	NM_006438.5	c.346+5G>A		splice_donor_5th_base_variant, intron_variant		ENST00000332843.3
COLEC10	NM_001324095.2	c.139+5G>A		splice_donor_5th_base_variant, intron_variant
COLEC10	XM_005250756.4	c.139+5G>A		splice_donor_5th_base_variant, intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
COLEC10	ENST00000332843.3	c.346+5G>A		splice_donor_5th_base_variant, intron_variant		1	NM_006438.5	P1
COLEC10	ENST00000521788.1	n.433+5G>A		splice_donor_5th_base_variant, intron_variant, non_coding_transcript_variant		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

GnomAD3 exomes AF: 0.00729 AC: 1809 AN: 248142 Hom.: 83 AF XY: 0.00562 AC XY: 754 AN XY: 134154

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 SAS exome AF: 0.000368

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

Gnomad4 AFR exome AF: 0.0903

Gnomad4 AMR exome AF: 0.00820

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000254

Gnomad4 SAS exome AF: 0.000306

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000132

Gnomad4 OTH exome AF: 0.00615

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

Gnomad4 AFR AF: 0.0877

Gnomad4 AMR AF: 0.0110

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000177

Gnomad4 OTH AF: 0.0194

Alfa AF: 0.00587 Hom.: 41

Bravo AF: 0.0288

Asia WGS AF: 0.00751 AC: 27 AN: 3478

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

Dec 31, 2019

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.74
Cadd	Benign	8.9
Dann	Benign	0.56

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

Publications

LitVar

Other links and lift over

dbSNP: rs73327239; hg19: chr8-120114645; COSMIC: COSV60521990;