6-37661874-G-T

Variant names:

• chr6-37661874-G-T
• rs10807187
• NM_153487.4:c.207+2093C>A

Variant summary

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

The NM_153487.4(MDGA1):​c.207+2093C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.355 in 151,992 control chromosomes in the GnomAD database, including 11,828 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 0.36 (11828 hom., cov: 31)
• Consequence: MDGA1 NM_153487.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.671
• Publications: 4 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=-0.89).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.489 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MDGA1	NM_153487.4	c.207+2093C>A		intron_variant	Intron 2 of 16	ENST00000434837.8	NP_705691.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MDGA1	ENST00000434837.8	c.207+2093C>A		intron_variant	Intron 2 of 16	1	NM_153487.4	ENSP00000402584.2

Frequencies

GnomAD3 genomes AF: 0.355 AC: 53986 AN: 151874 Hom.: 11834 Cov.: 31

Gnomad AFR AF: 0.0969

Gnomad AMI AF: 0.536

Gnomad AMR AF: 0.344

Gnomad ASJ AF: 0.415

Gnomad EAS AF: 0.263

Gnomad SAS AF: 0.368

Gnomad FIN AF: 0.506

Gnomad MID AF: 0.414

Gnomad NFE AF: 0.493

Gnomad OTH AF: 0.349

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

GnomAD4 genome AF: 0.355 AC: 53962 AN: 151992 Hom.: 11828 Cov.: 31 AF XY: 0.357 AC XY: 26527 AN XY: 74286

African (AFR) AF: 0.0967 AC: 4013 AN: 41512

American (AMR) AF: 0.343 AC: 5241 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.415 AC: 1438 AN: 3464

East Asian (EAS) AF: 0.263 AC: 1360 AN: 5180

South Asian (SAS) AF: 0.368 AC: 1772 AN: 4814

European-Finnish (FIN) AF: 0.506 AC: 5338 AN: 10546

Middle Eastern (MID) AF: 0.404 AC: 118 AN: 292

European-Non Finnish (NFE) AF: 0.493 AC: 33469 AN: 67892

Other (OTH) AF: 0.344 AC: 726 AN: 2108

Alfa AF: 0.437 Hom.: 5170

Bravo AF: 0.332

Asia WGS AF: 0.264 AC: 918 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	2.8
DANN	Benign	0.49
PhyloP100		0.67
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: rs10807187; hg19: chr6-37629650;