rs59819090

chr12-10125307-G-A

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

The NM_197947.3(CLEC7A):c.482C>T(p.Ser161Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00275 in 1,611,586 control chromosomes in the GnomAD database, including 72 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.014 (33 hom., cov: 32)
  • Exomes 𝑓: 0.0016 (39 hom.)
• Consequence: CLEC7A NM_197947.3 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.399

Genes affected

CLEC7A (HGNC:14558): (C-type lectin domain containing 7A) This gene encodes a member of the C-type lectin/C-type lectin-like domain (CTL/CTLD) superfamily. The encoded glycoprotein is a small type II membrane receptor with an extracellular C-type lectin-like domain fold and a cytoplasmic domain with an immunoreceptor tyrosine-based activation motif. It functions as a pattern-recognition receptor that recognizes a variety of beta-1,3-linked and beta-1,6-linked glucans from fungi and plants, and in this way plays a role in innate immune response. Alternate transcriptional splice variants, encoding different isoforms, have been characterized. This gene is closely linked to other CTL/CTLD superfamily members on chromosome 12p13 in the natural killer gene complex region. [provided by RefSeq, Jul 2008]

LOC105369655 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0029134154).
• BP6: Variant 12-10125307-G-A is Benign according to our data. Variant chr12-10125307-G-A is described in ClinVar as [Benign]. Clinvar id is 376808.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0138 (2099/151746) while in subpopulation AFR AF= 0.0467 (1934/41378). AF 95% confidence interval is 0.045. There are 33 homozygotes in gnomad4. There are 1042 alleles in male gnomad4 subpopulation. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 33 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CLEC7A	NM_197947.3	c.482C>T	p.Ser161Leu	missense_variant	4/6	ENST00000304084.13
LOC105369655	XR_007063208.1	n.182-5774G>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CLEC7A	ENST00000304084.13	c.482C>T	p.Ser161Leu	missense_variant	4/6	1	NM_197947.3	P4

Frequencies

GnomAD3 genomes AF: 0.0138 AC: 2088 AN: 151630 Hom.: 33 Cov.: 32

Gnomad AFR AF: 0.0466

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00762

Gnomad ASJ AF: 0.00375

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000209

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000206

Gnomad OTH AF: 0.00962

GnomAD3 exomes AF: 0.00369 AC: 928 AN: 251202 Hom.: 17 AF XY: 0.00274 AC XY: 372 AN XY: 135794

Gnomad AFR exome AF: 0.0483

Gnomad AMR exome AF: 0.00260

Gnomad ASJ exome AF: 0.00179

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000163

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000158

Gnomad OTH exome AF: 0.00196

GnomAD4 exome AF: 0.00160 AC: 2333 AN: 1459840 Hom.: 39 Cov.: 31 AF XY: 0.00137 AC XY: 996 AN XY: 726212

Gnomad4 AFR exome AF: 0.0517

Gnomad4 AMR exome AF: 0.00329

Gnomad4 ASJ exome AF: 0.00207

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000104

Gnomad4 FIN exome AF: 0.0000189

Gnomad4 NFE exome AF: 0.000157

Gnomad4 OTH exome AF: 0.00348

GnomAD4 genome AF: 0.0138 AC: 2099 AN: 151746 Hom.: 33 Cov.: 32 AF XY: 0.0141 AC XY: 1042 AN XY: 74132

Gnomad4 AFR AF: 0.0467

Gnomad4 AMR AF: 0.00761

Gnomad4 ASJ AF: 0.00375

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000209

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000206

Gnomad4 OTH AF: 0.00952

Alfa AF: 0.00288 Hom.: 12

Bravo AF: 0.0157

TwinsUK AF: 0.000270 AC: 1

ALSPAC AF: 0.00 AC: 0

ESP6500AA AF: 0.0472 AC: 208

ESP6500EA AF: 0.000233 AC: 2

ExAC AF: 0.00424 AC: 515

Asia WGS AF: 0.00318 AC: 11 AN: 3478

EpiCase AF: 0.000273

EpiControl AF: 0.000237

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics	Jan 10, 2017	- -
Benign, criteria provided, single submitter	clinical testing	Invitae	Aug 21, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.089
BayesDel_addAF	Benign	-0.69	T
BayesDel_noAF	Benign	-0.72
Cadd	Benign	9.2
Dann	Benign	0.91
Eigen	Benign	-0.81
Eigen_PC	Benign	-0.85
FATHMM_MKL	Benign	0.029	N
LIST_S2	Benign	0.79	T;T;T;T;T
MetaRNN	Benign	0.0029	T;T;T;T;T
MetaSVM	Benign	-1.0	T
MutationTaster	Benign	1.0	N;N;N;N;N
PrimateAI	Benign	0.27	T
PROVEAN	Benign	-2.3	N;D;D;N;N
REVEL	Benign	0.031
Sift	Benign	0.24	T;T;T;T;T
Sift4G	Benign	0.15	T;T;T;T;T
Polyphen		0.22	B;B;B;B;B
Vest4		0.25
MVP		0.29
MPC		0.031
ClinPred		0.0042	T
GERP RS		1.9
Varity_R		0.084
gMVP		0.33

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs59819090; hg19: chr12-10277906;