rs16910527

chr12-10118534-A-C

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_197947.3(CLEC7A):c.668T>G(p.Ile223Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00187 in 1,612,906 control chromosomes in the GnomAD database, including 46 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

• Frequency:
  • Genomes: 𝑓 0.010 (27 hom., cov: 32)
  • Exomes 𝑓: 0.0010 (19 hom.)
• Consequence: CLEC7A NM_197947.3 missense
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 3.48

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.003911674).
• BP6: Variant 12-10118534-A-C is Benign according to our data. Variant chr12-10118534-A-C is described in ClinVar as [Benign]. Clinvar id is 720451.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr12-10118534-A-C is described in Lovd as [Benign].
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0102 (1560/152338) while in subpopulation AFR AF= 0.0362 (1504/41566). AF 95% confidence interval is 0.0347. There are 27 homozygotes in gnomad4. There are 718 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 27 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CLEC7A	NM_197947.3	c.668T>G	p.Ile223Ser	missense_variant	6/6	ENST00000304084.13
LOC105369655	XR_007063208.1	n.181+2991A>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CLEC7A	ENST00000304084.13	c.668T>G	p.Ile223Ser	missense_variant	6/6	1	NM_197947.3	P4

Frequencies

GnomAD3 genomes AF: 0.0102 AC: 1558 AN: 152220 Hom.: 27 Cov.: 32

Gnomad AFR AF: 0.0362

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00275

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: 0.00430

GnomAD3 exomes AF: 0.00249 AC: 626 AN: 251372 Hom.: 9 AF XY: 0.00173 AC XY: 235 AN XY: 135862

Gnomad AFR exome AF: 0.0353

Gnomad AMR exome AF: 0.000839

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000544

Gnomad SAS exome AF: 0.0000653

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000132

Gnomad OTH exome AF: 0.000815

GnomAD4 exome AF: 0.000998 AC: 1458 AN: 1460568 Hom.: 19 Cov.: 31 AF XY: 0.000925 AC XY: 672 AN XY: 726704

Gnomad4 AFR exome AF: 0.0342

Gnomad4 AMR exome AF: 0.00123

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000252

Gnomad4 SAS exome AF: 0.000116

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000702

Gnomad4 OTH exome AF: 0.00255

GnomAD4 genome AF: 0.0102 AC: 1560 AN: 152338 Hom.: 27 Cov.: 32 AF XY: 0.00964 AC XY: 718 AN XY: 74496

Gnomad4 AFR AF: 0.0362

Gnomad4 AMR AF: 0.00274

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000735

Gnomad4 OTH AF: 0.00426

Alfa AF: 0.00496 Hom.: 9

Bravo AF: 0.0111

ESP6500AA AF: 0.0397 AC: 175

ESP6500EA AF: 0.00 AC: 0

ExAC AF: 0.00324 AC: 393

Asia WGS AF: 0.00318 AC: 11 AN: 3478

EpiCase AF: 0.000218

EpiControl AF: 0.000296

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

Mar 28, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.80
BayesDel_addAF	Benign	-0.55	T
BayesDel_noAF	Benign	-0.34
Cadd	Uncertain	25
Dann	Uncertain	0.99
Eigen	Uncertain	0.36
Eigen_PC	Uncertain	0.26
FATHMM_MKL	Uncertain	0.85	D
LIST_S2	Benign	0.37	T;T
MetaRNN	Benign	0.0039	T;T
MetaSVM	Benign	-1.1	T
MutationTaster	Benign	0.76	D;D;D;N;N
PROVEAN	Benign	0.48	N;N
REVEL	Benign	0.087
Sift	Pathogenic	0.0	D;D
Sift4G	Pathogenic	0.0	D;D
Polyphen		0.99	D;D
Vest4		0.17
MutPred		0.11		.;Loss of MoRF binding (P = 0.1412);
MVP		0.13
ClinPred		0.030	T
GERP RS		3.8

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: rs16910527; hg19: chr12-10271133;