8-119206063-C-T

Variant summary

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

The ENST00000522112.6(MAL2):c.-72-15524C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.554 in 151,880 control chromosomes in the GnomAD database, including 24,145 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 0.55 (24145 hom., cov: 31)
• Consequence: MAL2 ENST00000522112.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.26

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.891 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MAL2	ENST00000522112.6	c.-72-15524C>T		intron_variant		4

Frequencies

GnomAD3 genomes AF: 0.554 AC: 84067 AN: 151762 Hom.: 24098 Cov.: 31

Gnomad AFR AF: 0.607

Gnomad AMI AF: 0.418

Gnomad AMR AF: 0.611

Gnomad ASJ AF: 0.435

Gnomad EAS AF: 0.913

Gnomad SAS AF: 0.635

Gnomad FIN AF: 0.624

Gnomad MID AF: 0.456

Gnomad NFE AF: 0.475

Gnomad OTH AF: 0.505

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

GnomAD4 genome AF: 0.554 AC: 84166 AN: 151880 Hom.: 24145 Cov.: 31 AF XY: 0.567 AC XY: 42056 AN XY: 74238

Gnomad4 AFR AF: 0.607

Gnomad4 AMR AF: 0.611

Gnomad4 ASJ AF: 0.435

Gnomad4 EAS AF: 0.913

Gnomad4 SAS AF: 0.635

Gnomad4 FIN AF: 0.624

Gnomad4 NFE AF: 0.475

Gnomad4 OTH AF: 0.510

Alfa AF: 0.485 Hom.: 25552

Bravo AF: 0.553

Asia WGS AF: 0.763 AC: 2651 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
Cadd	Benign	0.11
Dann	Benign	0.61

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs9297594; hg19: chr8-120218302;