8-119212566-A-G

Variant names:

• chr8-119212566-A-G
• rs1364705
• NM_052886.3:c.132+3962A>G

Variant summary

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

The NM_052886.3(MAL2):​c.132+3962A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.211 in 152,206 control chromosomes in the GnomAD database, including 4,173 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 0.21 (4173 hom., cov: 32)
• Consequence: MAL2 NM_052886.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.105
• Publications: 13 publications found

Genes affected

MAL2 (HGNC:13634): (mal, T cell differentiation protein 2) This gene encodes a multispan transmembrane protein belonging to the MAL proteolipid family. The protein is a component of lipid rafts and, in polarized cells, it primarily localizes to endosomal structures beneath the apical membrane. It is required for transcytosis, an intracellular transport pathway used to deliver membrane-bound proteins and exogenous cargos from the basolateral to the apical surface. [provided by RefSeq, Jul 2008]

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 = 0.552 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_052886.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MAL2	NM_052886.3	MANE Select	c.132+3962A>G		intron	N/A	NP_443118.1	Q969L2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MAL2	ENST00000614891.5	TSL:1 MANE Select	c.132+3962A>G		intron	N/A	ENSP00000479708.1	Q969L2
	MAL2	ENST00000884403.1		c.132+3962A>G		intron	N/A	ENSP00000554462.1
	MAL2	ENST00000884404.1		c.132+3962A>G		intron	N/A	ENSP00000554463.1

Frequencies

GnomAD3 genomes AF: 0.212 AC: 32175 AN: 152088 Hom.: 4170 Cov.: 32

Gnomad AFR AF: 0.0850

Gnomad AMI AF: 0.171

Gnomad AMR AF: 0.281

Gnomad ASJ AF: 0.234

Gnomad EAS AF: 0.570

Gnomad SAS AF: 0.200

Gnomad FIN AF: 0.264

Gnomad MID AF: 0.237

Gnomad NFE AF: 0.238

Gnomad OTH AF: 0.214

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

GnomAD4 genome AF: 0.211 AC: 32180 AN: 152206 Hom.: 4173 Cov.: 32 AF XY: 0.219 AC XY: 16276 AN XY: 74402

African (AFR) AF: 0.0848 AC: 3525 AN: 41556

American (AMR) AF: 0.282 AC: 4311 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.234 AC: 812 AN: 3472

East Asian (EAS) AF: 0.569 AC: 2940 AN: 5166

South Asian (SAS) AF: 0.201 AC: 969 AN: 4824

European-Finnish (FIN) AF: 0.264 AC: 2791 AN: 10584

Middle Eastern (MID) AF: 0.231 AC: 68 AN: 294

European-Non Finnish (NFE) AF: 0.238 AC: 16164 AN: 67994

Other (OTH) AF: 0.210 AC: 444 AN: 2112

Alfa AF: 0.237 Hom.: 16689

Bravo AF: 0.210

Asia WGS AF: 0.316 AC: 1101 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	0.89
DANN	Benign	0.70
PhyloP100		-0.10
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: rs1364705; hg19: chr8-120224806;