chr8-119184776-G-C

Position:

• chr8-119184776-G-C

Variant summary

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

The ENST00000522112.6(MAL2):​c.-73+14992G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.53 in 151,858 control chromosomes in the GnomAD database, including 21,604 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 0.53 (21604 hom., cov: 31)
• Consequence: MAL2 ENST00000522112.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.158

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=-0.81).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.577 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LOC105375725	XR_928585.3	n.188+14992G>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MAL2	ENST00000522112.6	c.-73+14992G>C		intron_variant		4		ENSP00000483044.1

Frequencies

GnomAD3 genomes AF: 0.530 AC: 80405 AN: 151740 Hom.: 21596 Cov.: 31

Gnomad AFR AF: 0.583

Gnomad AMI AF: 0.566

Gnomad AMR AF: 0.473

Gnomad ASJ AF: 0.538

Gnomad EAS AF: 0.572

Gnomad SAS AF: 0.350

Gnomad FIN AF: 0.482

Gnomad MID AF: 0.589

Gnomad NFE AF: 0.525

Gnomad OTH AF: 0.554

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

GnomAD4 genome AF: 0.530 AC: 80444 AN: 151858 Hom.: 21604 Cov.: 31 AF XY: 0.525 AC XY: 38956 AN XY: 74232

Gnomad4 AFR AF: 0.583

Gnomad4 AMR AF: 0.473

Gnomad4 ASJ AF: 0.538

Gnomad4 EAS AF: 0.572

Gnomad4 SAS AF: 0.350

Gnomad4 FIN AF: 0.482

Gnomad4 NFE AF: 0.525

Gnomad4 OTH AF: 0.549

Alfa AF: 0.529 Hom.: 2691

Bravo AF: 0.532

Asia WGS AF: 0.472 AC: 1644 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	1.2
DANN	Benign	0.75

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs2432961; hg19: chr8-120197015;