rs1316873

Positions:

• chr2-95032901-C-G
• chr2-95032901-C-T

Variant summary

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

The NM_002371.4(MAL):​c.93+7016C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.123 in 152,202 control chromosomes in the GnomAD database, including 1,536 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 0.12 (1536 hom., cov: 32)
• Consequence: MAL NM_002371.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.676

Genes affected

MAL (HGNC:6817): (mal, T cell differentiation protein) The protein encoded by this gene is a highly hydrophobic integral membrane protein belonging to the MAL family of proteolipids. The protein has been localized to the endoplasmic reticulum of T-cells and is a candidate linker protein in T-cell signal transduction. In addition, this proteolipid is localized in compact myelin of cells in the nervous system and has been implicated in myelin biogenesis and/or function. The protein plays a role in the formation, stabilization and maintenance of glycosphingolipid-enriched membrane microdomains. Down-regulation of this gene has been associated with a variety of human epithelial malignancies. Alternative splicing produces four transcript variants which vary from each other by the presence or absence of alternatively spliced exons 2 and 3. [provided by RefSeq, May 2012]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.262 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MAL	NM_002371.4	c.93+7016C>G		intron_variant		ENST00000309988.9	NP_002362.1
MAL	NM_022438.3	c.93+7016C>G		intron_variant			NP_071883.1
MAL	NM_022439.3	c.93+7016C>G		intron_variant			NP_071884.1
MAL	NM_022440.3	c.93+7016C>G		intron_variant			NP_071885.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MAL	ENST00000309988.9	c.93+7016C>G		intron_variant		1	NM_002371.4	ENSP00000310880	P1

Frequencies

GnomAD3 genomes AF: 0.123 AC: 18748 AN: 152084 Hom.: 1530 Cov.: 32

Gnomad AFR AF: 0.0691

Gnomad AMI AF: 0.0989

Gnomad AMR AF: 0.268

Gnomad ASJ AF: 0.0995

Gnomad EAS AF: 0.265

Gnomad SAS AF: 0.137

Gnomad FIN AF: 0.145

Gnomad MID AF: 0.0981

Gnomad NFE AF: 0.110

Gnomad OTH AF: 0.128

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

GnomAD4 genome AF: 0.123 AC: 18764 AN: 152202 Hom.: 1536 Cov.: 32 AF XY: 0.127 AC XY: 9471 AN XY: 74412

Gnomad4 AFR AF: 0.0689

Gnomad4 AMR AF: 0.269

Gnomad4 ASJ AF: 0.0995

Gnomad4 EAS AF: 0.264

Gnomad4 SAS AF: 0.137

Gnomad4 FIN AF: 0.145

Gnomad4 NFE AF: 0.110

Gnomad4 OTH AF: 0.130

Alfa AF: 0.115 Hom.: 156

Bravo AF: 0.137

Asia WGS AF: 0.181 AC: 631 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	7.0
DANN	Benign	0.68

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: rs1316873; hg19: chr2-95698646;