6-37670786-C-T

Variant names:

• chr6-37670786-C-T
• rs7769372
• NM_153487.4:c.68-6680G>A

Variant summary

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

The ENST00000434837.8(MDGA1):​c.68-6680G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.177 in 152,034 control chromosomes in the GnomAD database, including 3,131 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 0.18 (3131 hom., cov: 32)
• Consequence: MDGA1 ENST00000434837.8 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0330
• Publications: 5 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 (EAS) allele frequency at 95% confidence interval = 0.341 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000434837.8. 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.68-6680G>A		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.68-6680G>A		intron	N/A	ENSP00000402584.2
	MDGA1	ENST00000505425.5	TSL:5	c.68-6680G>A		intron	N/A	ENSP00000422042.1
	MDGA1	ENST00000650466.1		c.68-6680G>A		intron	N/A	ENSP00000498018.1

Frequencies

GnomAD3 genomes AF: 0.177 AC: 26866 AN: 151914 Hom.: 3121 Cov.: 32

Gnomad AFR AF: 0.298

Gnomad AMI AF: 0.0603

Gnomad AMR AF: 0.169

Gnomad ASJ AF: 0.143

Gnomad EAS AF: 0.355

Gnomad SAS AF: 0.255

Gnomad FIN AF: 0.199

Gnomad MID AF: 0.209

Gnomad NFE AF: 0.0856

Gnomad OTH AF: 0.187

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

GnomAD4 genome AF: 0.177 AC: 26908 AN: 152034 Hom.: 3131 Cov.: 32 AF XY: 0.184 AC XY: 13663 AN XY: 74310

African (AFR) AF: 0.298 AC: 12339 AN: 41430

American (AMR) AF: 0.169 AC: 2583 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.143 AC: 496 AN: 3468

East Asian (EAS) AF: 0.355 AC: 1828 AN: 5152

South Asian (SAS) AF: 0.256 AC: 1231 AN: 4816

European-Finnish (FIN) AF: 0.199 AC: 2100 AN: 10562

Middle Eastern (MID) AF: 0.211 AC: 62 AN: 294

European-Non Finnish (NFE) AF: 0.0856 AC: 5819 AN: 68006

Other (OTH) AF: 0.187 AC: 395 AN: 2116

Alfa AF: 0.111 Hom.: 2026

Bravo AF: 0.182

Asia WGS AF: 0.294 AC: 1021 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	1.2
DANN	Benign	0.65
PhyloP100		-0.033
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: rs7769372; hg19: chr6-37638562;