Genetic Variant MLXIPL:c.2058+41G>A (chr7-73596112-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The NM_032951.3(MLXIPL):c.2058+41G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.176 in 1,605,758 control chromosomes in the GnomAD database, including 26,324 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 0.15 ( 1864 hom., cov: 30)

Exomes 𝑓: 0.18 ( 24460 hom. )

Consequence

MLXIPL
NM_032951.3 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.151

Publications

32 publications found

Variant links:

Genes affected

MLXIPL (HGNC:12744): (MLX interacting protein like) This gene encodes a basic helix-loop-helix leucine zipper transcription factor of the Myc/Max/Mad superfamily. This protein forms a heterodimeric complex and binds and activates, in a glucose-dependent manner, carbohydrate response element (ChoRE) motifs in the promoters of triglyceride synthesis genes. The gene is deleted in Williams-Beuren syndrome, a multisystem developmental disorder caused by the deletion of contiguous genes at chromosome 7q11.23. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Dec 2015]

MLXIPL 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=-0.82).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.188 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MLXIPL	NM_032951.3 link	c.2058+41G>A		intron_variant	Intron 13 of 16	ENST00000313375.8	NP_116569.1	Q9NP71-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MLXIPL	ENST00000313375.8 link	c.2058+41G>A		intron_variant	Intron 13 of 16	1	NM_032951.3	ENSP00000320886.3		Q9NP71-1

Frequencies

GnomAD3 genomes

AF:

0.149

AC:

22610

AN:

151770

Hom.:

1863

Cov.:

show subpopulations

Gnomad AFR

AF:

0.101

Gnomad AMI

AF:

0.151

Gnomad AMR

AF:

0.117

Gnomad ASJ

AF:

0.166

Gnomad EAS

AF:

0.0992

Gnomad SAS

AF:

0.0999

Gnomad FIN

AF:

0.159

Gnomad MID

AF:

0.158

Gnomad NFE

AF:

0.190

Gnomad OTH

AF:

0.145

GnomAD2 exomes

AF:

0.148

AC:

35583

AN:

240544

AF XY:

0.149

show subpopulations

Gnomad AFR exome

AF:

0.0959

Gnomad AMR exome

AF:

0.0915

Gnomad ASJ exome

AF:

0.164

Gnomad EAS exome

AF:

0.0930

Gnomad FIN exome

AF:

0.172

Gnomad NFE exome

AF:

0.188

Gnomad OTH exome

AF:

0.157

GnomAD4 exome

AF:

0.179

AC:

260122

AN:

1453870

Hom.:

24460

Cov.:

AF XY:

0.177

AC XY:

127888

AN XY:

722812

show subpopulations

African (AFR)

AF:

0.0970

AC:

3238

AN:

33372

American (AMR)

AF:

0.0938

AC:

4164

AN:

44412

Ashkenazi Jewish (ASJ)

AF:

0.167

AC:

4351

AN:

26088

East Asian (EAS)

AF:

0.0958

AC:

3797

AN:

39628

South Asian (SAS)

AF:

0.104

AC:

8972

AN:

86040

European-Finnish (FIN)

AF:

0.174

AC:

8661

AN:

49756

Middle Eastern (MID)

AF:

0.159

AC:

723

AN:

4556

European-Non Finnish (NFE)

AF:

0.195

AC:

216192

AN:

1109936

Other (OTH)

AF:

0.167

AC:

10024

AN:

60082

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.486

Heterozygous variant carriers

12183

24366

36549

48732

60915

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

7448

14896

22344

29792

37240

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.149

AC:

22622

AN:

151888

Hom.:

1864

Cov.:

AF XY:

0.147

AC XY:

10914

AN XY:

74210

show subpopulations

African (AFR)

AF:

0.101

AC:

4169

AN:

41436

American (AMR)

AF:

0.117

AC:

1780

AN:

15252

Ashkenazi Jewish (ASJ)

AF:

0.166

AC:

575

AN:

3468

East Asian (EAS)

AF:

0.0997

AC:

514

AN:

5158

South Asian (SAS)

AF:

0.100

AC:

481

AN:

4800

European-Finnish (FIN)

AF:

0.159

AC:

1681

AN:

10574

Middle Eastern (MID)

AF:

0.153

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.190

AC:

12926

AN:

67888

Other (OTH)

AF:

0.149

AC:

313

AN:

2106

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.495

Heterozygous variant carriers

937

1874

2812

3749

4686

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

242

484

726

968

1210

<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:

0.166

Hom.:

430

Bravo

AF:

0.143

Asia WGS

AF:

0.110

AC:

384

AN:

3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.82

CADD

Benign

3.4

(source)

DANN

Benign

0.82

PhyloP100

-0.15

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over