rs1364705

chr8-119212566-A-G

Variant summary

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

The NM_052886.3(MAL2):c.132+3962A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.211 in 152,206 control chromosomes in the GnomAD database, including 4,173 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 0.21 (4173 hom., cov: 32)
• Consequence: MAL2 NM_052886.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.105

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=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.552 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MAL2	NM_052886.3	c.132+3962A>G		intron_variant		ENST00000614891.5
MAL2	XM_011516807.3	c.132+3962A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MAL2	ENST00000614891.5	c.132+3962A>G		intron_variant		1	NM_052886.3	P1
MAL2	ENST00000522112.6	c.-72-9021A>G		intron_variant		4
MAL2	ENST00000531508.1	c.-73+3366A>G		intron_variant		3
MAL2	ENST00000534619.5	c.-73+4473A>G		intron_variant		4

Frequencies

GnomAD3 genomes AF: 0.212 AC: 32175 AN: 152088 Hom.: 4170 Cov.: 32

Gnomad AFR AF: 0.0850

Gnomad AMI AF: 0.171

Gnomad AMR AF: 0.281

Gnomad ASJ AF: 0.234

Gnomad EAS AF: 0.570

Gnomad SAS AF: 0.200

Gnomad FIN AF: 0.264

Gnomad MID AF: 0.237

Gnomad NFE AF: 0.238

Gnomad OTH AF: 0.214

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

GnomAD4 genome AF: 0.211 AC: 32180 AN: 152206 Hom.: 4173 Cov.: 32 AF XY: 0.219 AC XY: 16276 AN XY: 74402

Gnomad4 AFR AF: 0.0848

Gnomad4 AMR AF: 0.282

Gnomad4 ASJ AF: 0.234

Gnomad4 EAS AF: 0.569

Gnomad4 SAS AF: 0.201

Gnomad4 FIN AF: 0.264

Gnomad4 NFE AF: 0.238

Gnomad4 OTH AF: 0.210

Alfa AF: 0.244 Hom.: 7668

Bravo AF: 0.210

Asia WGS AF: 0.316 AC: 1101 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
Cadd	Benign	0.89
Dann	Benign	0.70

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs1364705; hg19: chr8-120224806;