8-119186754-A-G

Variant names:

• chr8-119186754-A-G
• rs2432960
• ENST00000522112.6:c.-73+16970A>G

Variant summary

Our verdict is Benign. The variant received -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
• 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=-0.9).
• 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 rank	MANE	Protein	UniProt
LOC105375725	XR_928585.3	n.189-16736A>G		intron_variant	Intron 2 of 2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MAL2	ENST00000522112.6	c.-73+16970A>G		intron_variant	Intron 2 of 4	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

African (AFR) AF: 0.616 AC: 25521 AN: 41430

American (AMR) AF: 0.467 AC: 7128 AN: 15256

Ashkenazi Jewish (ASJ) AF: 0.588 AC: 2042 AN: 3470

East Asian (EAS) AF: 0.643 AC: 3323 AN: 5166

South Asian (SAS) AF: 0.452 AC: 2176 AN: 4812

European-Finnish (FIN) AF: 0.362 AC: 3830 AN: 10570

Middle Eastern (MID) AF: 0.609 AC: 179 AN: 294

European-Non Finnish (NFE) AF: 0.482 AC: 32780 AN: 67944

Other (OTH) AF: 0.536 AC: 1131 AN: 2110

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
PhyloP100		-0.18

Splicing

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

Other links and lift over

dbSNP: rs2432960; hg19: chr8-120198993;