8-119186754-A-G

Position:

• chr8-119186754-A-G

Variant summary

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

The ENST00000522112.6(MAL2):​c.-73+16970A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.517 in 151,962 control chromosomes in the GnomAD database, including 20,953 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 0.52 (20953 hom., cov: 32)
• Consequence: MAL2 ENST00000522112.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.183

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=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.625 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LOC105375725	XR_928585.3	n.189-16736A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MAL2	ENST00000522112.6	c.-73+16970A>G		intron_variant		4		ENSP00000483044.1

Frequencies

GnomAD3 genomes AF: 0.517 AC: 78484 AN: 151844 Hom.: 20953 Cov.: 32

Gnomad AFR AF: 0.616

Gnomad AMI AF: 0.447

Gnomad AMR AF: 0.468

Gnomad ASJ AF: 0.588

Gnomad EAS AF: 0.643

Gnomad SAS AF: 0.452

Gnomad FIN AF: 0.362

Gnomad MID AF: 0.608

Gnomad NFE AF: 0.482

Gnomad OTH AF: 0.542

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

GnomAD4 genome AF: 0.517 AC: 78517 AN: 151962 Hom.: 20953 Cov.: 32 AF XY: 0.510 AC XY: 37907 AN XY: 74274

Gnomad4 AFR AF: 0.616

Gnomad4 AMR AF: 0.467

Gnomad4 ASJ AF: 0.588

Gnomad4 EAS AF: 0.643

Gnomad4 SAS AF: 0.452

Gnomad4 FIN AF: 0.362

Gnomad4 NFE AF: 0.482

Gnomad4 OTH AF: 0.536

Alfa AF: 0.406 Hom.: 1392

Bravo AF: 0.527

Asia WGS AF: 0.548 AC: 1908 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	1.7
DANN	Benign	0.66

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs2432960; hg19: chr8-120198993;