8-119170870-T-C

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 2 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]

LOC105375725 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000522112.6. 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
There are no transcript annotations for this variant.

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MAL2	ENST00000522112.6	TSL:4	c.-73+1086T>C		intron	N/A	ENSP00000483044.1	A0A087WZL1

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

African (AFR) AF: 0.875 AC: 36299 AN: 41504

American (AMR) AF: 0.633 AC: 9657 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.733 AC: 2544 AN: 3472

East Asian (EAS) AF: 0.688 AC: 3530 AN: 5128

South Asian (SAS) AF: 0.592 AC: 2848 AN: 4812

European-Finnish (FIN) AF: 0.641 AC: 6788 AN: 10588

Middle Eastern (MID) AF: 0.776 AC: 228 AN: 294

European-Non Finnish (NFE) AF: 0.662 AC: 44995 AN: 67944

Other (OTH) AF: 0.741 AC: 1561 AN: 2106

Alfa AF: 0.626 Hom.: 2223

Bravo AF: 0.722

Asia WGS AF: 0.705 AC: 2455 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	6.3
DANN	Benign	0.55
PhyloP100		-0.12

Splicing

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

Other links and lift over

dbSNP: rs1549415; hg19: chr8-120183109;