8-119170870-T-C

Variant names:

• chr8-119170870-T-C
• rs1549415
• ENST00000522112.6:c.-73+1086T>C

Variant summary

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

The ENST00000522112.6(MAL2):​c.-73+1086T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.717 in 152,024 control chromosomes in the GnomAD database, including 39,974 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 0.72 (39974 hom., cov: 31)
• Consequence: MAL2 ENST00000522112.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.118

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]

LOC105375725 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.99).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.867 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LOC105375725	XR_928585.3	n.188+1086T>C		intron_variant	Intron 2 of 2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MAL2	ENST00000522112.6	c.-73+1086T>C		intron_variant	Intron 2 of 4	4		ENSP00000483044.1

Frequencies

GnomAD3 genomes AF: 0.717 AC: 108879 AN: 151906 Hom.: 39922 Cov.: 31

Gnomad AFR AF: 0.874

Gnomad AMI AF: 0.586

Gnomad AMR AF: 0.633

Gnomad ASJ AF: 0.733

Gnomad EAS AF: 0.688

Gnomad SAS AF: 0.593

Gnomad FIN AF: 0.641

Gnomad MID AF: 0.775

Gnomad NFE AF: 0.662

Gnomad OTH AF: 0.737

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

GnomAD4 genome AF: 0.717 AC: 108984 AN: 152024 Hom.: 39974 Cov.: 31 AF XY: 0.713 AC XY: 53011 AN XY: 74320

Gnomad4 AFR AF: 0.875

Gnomad4 AMR AF: 0.633

Gnomad4 ASJ AF: 0.733

Gnomad4 EAS AF: 0.688

Gnomad4 SAS AF: 0.592

Gnomad4 FIN AF: 0.641

Gnomad4 NFE AF: 0.662

Gnomad4 OTH AF: 0.741

Alfa AF: 0.605 Hom.: 1928

Bravo AF: 0.722

Asia WGS AF: 0.705 AC: 2455 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	6.3
DANN	Benign	0.55

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs1549415; hg19: chr8-120183109;