Genetic Variant NM_002371.4:c.93+7016C>G (chr2-95032901-C-G) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

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

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.676

Publications

7 publications found

Variant links:

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]

MAL links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002371.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
MAL	NM_002371.4	MANE Select	c.93+7016C>G	intron	N/A	NP_002362.1	P21145-1
MAL	NM_022438.3		c.93+7016C>G	intron	N/A	NP_071883.1	P21145-2
MAL	NM_022439.3		c.93+7016C>G	intron	N/A	NP_071884.1	P21145-3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
MAL	ENST00000309988.9	TSL:1 MANE Select	c.93+7016C>G	intron	N/A	ENSP00000310880.4	P21145-1
MAL	ENST00000353004.7	TSL:1	c.93+7016C>G	intron	N/A	ENSP00000306568.4	P21145-2
MAL	ENST00000354078.7	TSL:1	c.93+7016C>G	intron	N/A	ENSP00000304924.3	P21145-3

Frequencies

GnomAD3 genomes

AF:

0.123

AC:

18748

AN:

152084

Hom.:

1530

Cov.:

show subpopulations

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.:

AF XY:

0.127

AC XY:

9471

AN XY:

74412

show subpopulations

African (AFR)

AF:

0.0689

AC:

2862

AN:

41548

American (AMR)

AF:

0.269

AC:

4107

AN:

15294

Ashkenazi Jewish (ASJ)

AF:

0.0995

AC:

345

AN:

3468

East Asian (EAS)

AF:

0.264

AC:

1366

AN:

5170

South Asian (SAS)

AF:

0.137

AC:

659

AN:

4820

European-Finnish (FIN)

AF:

0.145

AC:

1534

AN:

10592

Middle Eastern (MID)

AF:

0.0952

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.110

AC:

7497

AN:

67990

Other (OTH)

AF:

0.130

AC:

276

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

822

1644

2465

3287

4109

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

208

416

624

832

1040

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

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 v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.80

CADD

Benign

7.0

(source)

DANN

Benign

0.68

PhyloP100

0.68

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over