rs7254215

Variant names:

• chr19-14602681-G-A
• rs7254215
• NM_001204118.2:c.894+2499G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001204118.2(CLEC17A):​c.894+2499G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.832 in 152,082 control chromosomes in the GnomAD database, including 53,401 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.83 (53401 hom., cov: 31)
• Consequence: CLEC17A NM_001204118.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.67
• Publications: 9 publications found

Genes affected

CLEC17A (HGNC:34520): (C-type lectin domain containing 17A) Enables fucose binding activity; identical protein binding activity; and mannose binding activity. Located in cell surface. [provided by Alliance of Genome Resources, Apr 2022]

ADGRE3 (HGNC:23647): (adhesion G protein-coupled receptor E3) This gene encodes a member of the class B seven-span transmembrane (TM7) receptor family expressed predominantly by cells of the immune system. Family members are characterized by an extended extracellular region with a variable number of N-terminal epidermal growth factor (EGF)-like domains coupled to a TM7 domain via a mucin-like spacer domain. This gene is closely linked to the gene encoding egf-like molecule containing mucin-like hormone receptor 2 on chromosome 19. This protein may play a role in myeloid-myeloid interactions during immune and inflammatory responses. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Jan 2014]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.99).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.943 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001204118.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CLEC17A	NM_001204118.2	MANE Select	c.894+2499G>A		intron	N/A	NP_001191047.1
	CLEC17A	NM_207390.4		c.894+2499G>A		intron	N/A	NP_997273.3
	CLEC17A	NR_109784.2		n.1034+2499G>A		intron	N/A

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CLEC17A	ENST00000417570.6	TSL:1 MANE Select	c.894+2499G>A		intron	N/A	ENSP00000393719.2
	CLEC17A	ENST00000339847.9	TSL:1	n.742+2869G>A		intron	N/A	ENSP00000341620.5
	CLEC17A	ENST00000551730.1	TSL:1	n.*273+2499G>A		intron	N/A	ENSP00000447424.1

Frequencies

GnomAD3 genomes AF: 0.832 AC: 126451 AN: 151964 Hom.: 53349 Cov.: 31

Gnomad AFR AF: 0.951

Gnomad AMI AF: 0.910

Gnomad AMR AF: 0.719

Gnomad ASJ AF: 0.832

Gnomad EAS AF: 0.511

Gnomad SAS AF: 0.754

Gnomad FIN AF: 0.796

Gnomad MID AF: 0.775

Gnomad NFE AF: 0.820

Gnomad OTH AF: 0.828

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.832 AC: 126563 AN: 152082 Hom.: 53401 Cov.: 31 AF XY: 0.825 AC XY: 61314 AN XY: 74324

African (AFR) AF: 0.951 AC: 39508 AN: 41528

American (AMR) AF: 0.719 AC: 10960 AN: 15254

Ashkenazi Jewish (ASJ) AF: 0.832 AC: 2890 AN: 3472

East Asian (EAS) AF: 0.511 AC: 2635 AN: 5152

South Asian (SAS) AF: 0.755 AC: 3644 AN: 4824

European-Finnish (FIN) AF: 0.796 AC: 8389 AN: 10540

Middle Eastern (MID) AF: 0.769 AC: 226 AN: 294

European-Non Finnish (NFE) AF: 0.820 AC: 55747 AN: 67998

Other (OTH) AF: 0.823 AC: 1736 AN: 2110

Alfa AF: 0.827 Hom.: 52139

Bravo AF: 0.830

Asia WGS AF: 0.626 AC: 2177 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	0.50
DANN	Benign	0.25
PhyloP100		-1.7
Mutation Taster		=100/0	polymorphism (auto)

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: rs7254215; hg19: chr19-14713493;