rs11759115

Variant names:

• chr6-37673254-T-C
• rs11759115
• NM_153487.4:c.68-9148A>G

Variant summary

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

The NM_153487.4(MDGA1):​c.68-9148A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.147 in 152,104 control chromosomes in the GnomAD database, including 1,814 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 0.15 (1814 hom., cov: 32)
• Consequence: MDGA1 NM_153487.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.216
• Publications: 6 publications found

Genes affected

MDGA1 (HGNC:19267): (MAM domain containing glycosylphosphatidylinositol anchor 1) This gene encodes a glycosylphosphatidylinositol (GPI)-anchored cell surface glycoprotein that is expressed predominantly in the developing nervous system. In addition to possessing several cell adhesion molecule-like domains, the mature protein has six Ig-like domains, a single fibronectin type III domain, a MAM domain and a C-terminal GPI-anchoring site. Studies in other mammals suggest this protein plays a role in cell adhesion, migration, and axon guidance and, in the developing brain, neuronal migration. In humans, this gene is associated with bipolar disorder and schizophrenia. [provided by RefSeq, Oct 2016]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.198 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_153487.4. 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
	MDGA1	NM_153487.4	MANE Select	c.68-9148A>G		intron	N/A	NP_705691.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MDGA1	ENST00000434837.8	TSL:1 MANE Select	c.68-9148A>G		intron	N/A	ENSP00000402584.2
	MDGA1	ENST00000505425.5	TSL:5	c.68-9148A>G		intron	N/A	ENSP00000422042.1
	MDGA1	ENST00000650466.1		c.68-9148A>G		intron	N/A	ENSP00000498018.1

Frequencies

GnomAD3 genomes AF: 0.147 AC: 22269 AN: 151986 Hom.: 1802 Cov.: 32

Gnomad AFR AF: 0.107

Gnomad AMI AF: 0.246

Gnomad AMR AF: 0.204

Gnomad ASJ AF: 0.0941

Gnomad EAS AF: 0.154

Gnomad SAS AF: 0.147

Gnomad FIN AF: 0.171

Gnomad MID AF: 0.104

Gnomad NFE AF: 0.155

Gnomad OTH AF: 0.142

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

GnomAD4 genome AF: 0.147 AC: 22302 AN: 152104 Hom.: 1814 Cov.: 32 AF XY: 0.146 AC XY: 10831 AN XY: 74344

African (AFR) AF: 0.107 AC: 4436 AN: 41510

American (AMR) AF: 0.204 AC: 3117 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.0941 AC: 326 AN: 3466

East Asian (EAS) AF: 0.154 AC: 793 AN: 5160

South Asian (SAS) AF: 0.147 AC: 709 AN: 4812

European-Finnish (FIN) AF: 0.171 AC: 1806 AN: 10576

Middle Eastern (MID) AF: 0.102 AC: 30 AN: 294

European-Non Finnish (NFE) AF: 0.155 AC: 10545 AN: 67984

Other (OTH) AF: 0.150 AC: 316 AN: 2106

Alfa AF: 0.153 Hom.: 7867

Bravo AF: 0.150

Asia WGS AF: 0.191 AC: 663 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	0.71
DANN	Benign	0.29
PhyloP100		-0.22
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: rs11759115; hg19: chr6-37641030;