dbSNP rs1051921: MLXIPL:n.*932C>T (chr7-73593613-G-A) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The ENST00000345114.9(MLXIPL):n.*932C>T variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.156 in 475,522 control chromosomes in the GnomAD database, including 6,387 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 ( 1858 hom., cov: 31)

Exomes 𝑓: 0.16 ( 4529 hom. )

Consequence

MLXIPL
ENST00000345114.9 non_coding_transcript_exon

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.597

Publications

28 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:

Genome browser will be placed here

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=-0.74).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.187 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MLXIPL	NM_032951.3 link	c.*252C>T		3_prime_UTR_variant	Exon 17 of 17	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.*252C>T		3_prime_UTR_variant	Exon 17 of 17	1	NM_032951.3	ENSP00000320886.3		Q9NP71-1

Frequencies

GnomAD3 genomes

AF:

0.149

AC:

22579

AN:

151996

Hom.:

1857

Cov.:

show subpopulations

Gnomad AFR

AF:

0.101

Gnomad AMI

AF:

0.154

Gnomad AMR

AF:

0.117

Gnomad ASJ

AF:

0.166

Gnomad EAS

AF:

0.0982

Gnomad SAS

AF:

0.0998

Gnomad FIN

AF:

0.160

Gnomad MID

AF:

0.158

Gnomad NFE

AF:

0.190

Gnomad OTH

AF:

0.143

GnomAD4 exome

AF:

0.159

AC:

51500

AN:

323410

Hom.:

4529

Cov.:

AF XY:

0.155

AC XY:

26681

AN XY:

171766

show subpopulations

African (AFR)

AF:

0.0944

AC:

881

AN:

9334

American (AMR)

AF:

0.105

AC:

1566

AN:

14846

Ashkenazi Jewish (ASJ)

AF:

0.165

AC:

1586

AN:

9614

East Asian (EAS)

AF:

0.0936

AC:

1837

AN:

19618

South Asian (SAS)

AF:

0.104

AC:

4559

AN:

43764

European-Finnish (FIN)

AF:

0.173

AC:

3126

AN:

18104

Middle Eastern (MID)

AF:

0.144

AC:

190

AN:

1316

European-Non Finnish (NFE)

AF:

0.185

AC:

34889

AN:

188718

Other (OTH)

AF:

0.158

AC:

2866

AN:

18096

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

2102

4205

6307

8410

10512

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

178

356

534

712

890

<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:

22590

AN:

152112

Hom.:

1858

Cov.:

AF XY:

0.147

AC XY:

10905

AN XY:

74358

show subpopulations

African (AFR)

AF:

0.100

AC:

4167

AN:

41490

American (AMR)

AF:

0.116

AC:

1776

AN:

15280

Ashkenazi Jewish (ASJ)

AF:

0.166

AC:

576

AN:

3468

East Asian (EAS)

AF:

0.0986

AC:

511

AN:

5180

South Asian (SAS)

AF:

0.100

AC:

481

AN:

4808

European-Finnish (FIN)

AF:

0.160

AC:

1692

AN:

10588

Middle Eastern (MID)

AF:

0.153

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.190

AC:

12894

AN:

67982

Other (OTH)

AF:

0.146

AC:

308

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

978

1955

2933

3910

4888

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.:

2359

Bravo

AF:

0.142

Asia WGS

AF:

0.107

AC:

373

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.74

CADD

Benign

4.0

(source)

DANN

Benign

0.86

PhyloP100

0.60

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over