rs12539499

Positions:

• chr7-141930467-T-C
• chr7-141930467-T-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_013252.3(CLEC5A):​c.453-249A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.235 in 152,150 control chromosomes in the GnomAD database, including 4,998 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 0.23 (4998 hom., cov: 32)
• Consequence: CLEC5A NM_013252.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.506

Genes affected

CLEC5A (HGNC:2054): (C-type lectin domain containing 5A) This gene encodes a member of the C-type lectin/C-type lectin-like domain (CTL/CTLD) superfamily. Members of this family share a common protein fold and have diverse functions, such as cell adhesion, cell-cell signalling, glycoprotein turnover, and roles in inflammation and immune response. The encoded type II transmembrane protein interacts with dnax-activation protein 12 and may play a role in cell activation. Alternative splice variants have been described but their full-length sequence has not been determined. [provided by RefSeq, Jul 2008]

LOC124901761 (HGNC:):

MGAM (HGNC:7043): (maltase-glucoamylase) This gene encodes maltase-glucoamylase, which is a brush border membrane enzyme that plays a role in the final steps of digestion of starch. The protein has two catalytic sites identical to those of sucrase-isomaltase, but the proteins are only 59% homologous. Both are members of glycosyl hydrolase family 31, which has a variety of substrate specificities. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.439 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CLEC5A	NM_013252.3	c.453-249A>G		intron_variant		ENST00000546910.6
LOC124901761	XR_007060564.1	n.89+447T>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CLEC5A	ENST00000546910.6	c.453-249A>G		intron_variant		1	NM_013252.3	P4

Frequencies

GnomAD3 genomes AF: 0.235 AC: 35703 AN: 152032 Hom.: 4999 Cov.: 32

Gnomad AFR AF: 0.0871

Gnomad AMI AF: 0.144

Gnomad AMR AF: 0.317

Gnomad ASJ AF: 0.266

Gnomad EAS AF: 0.455

Gnomad SAS AF: 0.235

Gnomad FIN AF: 0.274

Gnomad MID AF: 0.259

Gnomad NFE AF: 0.283

Gnomad OTH AF: 0.246

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

GnomAD4 genome AF: 0.235 AC: 35702 AN: 152150 Hom.: 4998 Cov.: 32 AF XY: 0.237 AC XY: 17611 AN XY: 74354

Gnomad4 AFR AF: 0.0870

Gnomad4 AMR AF: 0.317

Gnomad4 ASJ AF: 0.266

Gnomad4 EAS AF: 0.454

Gnomad4 SAS AF: 0.236

Gnomad4 FIN AF: 0.274

Gnomad4 NFE AF: 0.283

Gnomad4 OTH AF: 0.250

Alfa AF: 0.265 Hom.: 4153

Bravo AF: 0.235

Asia WGS AF: 0.346 AC: 1204 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.86
DANN	Benign	0.30

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: rs12539499; hg19: chr7-141630267;