chr8-119184776-G-C

Variant names:

• chr8-119184776-G-C
• rs2432961
• ENST00000522112.6:c.-73+14992G>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+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
• Publications: 4 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=-0.81).
• 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 rank	MANE	Protein	UniProt
LOC105375725	XR_928585.3	n.188+14992G>C		intron_variant	Intron 2 of 2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MAL2	ENST00000522112.6	c.-73+14992G>C		intron_variant	Intron 2 of 4	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

African (AFR) AF: 0.583 AC: 24143 AN: 41398

American (AMR) AF: 0.473 AC: 7214 AN: 15258

Ashkenazi Jewish (ASJ) AF: 0.538 AC: 1866 AN: 3470

East Asian (EAS) AF: 0.572 AC: 2934 AN: 5126

South Asian (SAS) AF: 0.350 AC: 1685 AN: 4814

European-Finnish (FIN) AF: 0.482 AC: 5091 AN: 10558

Middle Eastern (MID) AF: 0.592 AC: 174 AN: 294

European-Non Finnish (NFE) AF: 0.525 AC: 35670 AN: 67932

Other (OTH) AF: 0.549 AC: 1152 AN: 2098

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
PhyloP100		-0.16

Splicing

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

Other links and lift over

dbSNP: rs2432961; hg19: chr8-120197015;