dbSNP rs2281819: MLN:c.-8+57A>T (chr6-33803896-T-A) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The NM_002418.3(MLN):c.-8+57A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.226 in 152,380 control chromosomes in the GnomAD database, including 4,135 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 0.23 ( 4131 hom., cov: 32)

Exomes 𝑓: 0.16 ( 4 hom. )

Consequence

MLN
NM_002418.3 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.0680

Publications

10 publications found

Variant links:

Genes affected

MLN (HGNC:7141): (motilin) This gene encodes a small peptide hormone that is secreted by cells of the small intestine to regulate gastrointestinal contractions and motility. Proteolytic processing of the secreted protein produces the mature peptide and a byproduct referred to as motilin-associated peptide (MAP). Three transcript variants encoding different preproprotein isoforms but the same mature peptide have been found for this gene. [provided by RefSeq, May 2010]

MLN 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=-0.87).

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.317 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002418.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
MLN	NM_002418.3	MANE Select	c.-8+57A>T	intron	N/A	NP_002409.1
MLN	NM_001040109.2		c.-8+57A>T	intron	N/A	NP_001035198.1
MLN	NM_001184698.2		c.-8+57A>T	intron	N/A	NP_001171627.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
MLN	ENST00000430124.7	TSL:1 MANE Select	c.-8+57A>T	intron	N/A	ENSP00000388825.2
MLN	ENST00000507738.1	TSL:1	c.-8+57A>T	intron	N/A	ENSP00000425467.1
MLN	ENST00000266003.9	TSL:5	c.-8+57A>T	intron	N/A	ENSP00000266003.5

Frequencies

GnomAD3 genomes

AF:

0.226

AC:

34330

AN:

152060

Hom.:

4124

Cov.:

show subpopulations

Gnomad AFR

AF:

0.176

Gnomad AMI

AF:

0.195

Gnomad AMR

AF:

0.324

Gnomad ASJ

AF:

0.244

Gnomad EAS

AF:

0.164

Gnomad SAS

AF:

0.213

Gnomad FIN

AF:

0.308

Gnomad MID

AF:

0.193

Gnomad NFE

AF:

0.227

Gnomad OTH

AF:

0.198

GnomAD4 exome

AF:

0.163

AC:

AN:

202

Hom.:

AF XY:

0.134

AC XY:

AN XY:

134

show subpopulations

African (AFR)

AF:

0.125

AC:

AN:

American (AMR)

AF:

0.500

AC:

AN:

Ashkenazi Jewish (ASJ)

AF:

0.500

AC:

AN:

East Asian (EAS)

AF:

0.00

AC:

AN:

South Asian (SAS)

AF:

0.00

AC:

AN:

European-Finnish (FIN)

AF:

0.167

AC:

AN:

Middle Eastern (MID)

AF:

0.00

AC:

AN:

European-Non Finnish (NFE)

AF:

0.173

AC:

AN:

156

Other (OTH)

AF:

0.143

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.523

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<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:

0.226

AC:

34346

AN:

152178

Hom.:

4131

Cov.:

AF XY:

0.233

AC XY:

17370

AN XY:

74408

show subpopulations

African (AFR)

AF:

0.176

AC:

7292

AN:

41522

American (AMR)

AF:

0.324

AC:

4956

AN:

15282

Ashkenazi Jewish (ASJ)

AF:

0.244

AC:

847

AN:

3470

East Asian (EAS)

AF:

0.163

AC:

844

AN:

5174

South Asian (SAS)

AF:

0.214

AC:

1030

AN:

4818

European-Finnish (FIN)

AF:

0.308

AC:

3266

AN:

10588

Middle Eastern (MID)

AF:

0.184

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.227

AC:

15467

AN:

68006

Other (OTH)

AF:

0.195

AC:

412

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1368

2736

4103

5471

6839

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

354

708

1062

1416

1770

<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:

0.229

Hom.:

471

Bravo

AF:

0.225

Asia WGS

AF:

0.186

AC:

647

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.87

CADD

Benign

2.4

(source)

DANN

Benign

0.60

PhyloP100

-0.068

PromoterAI

-0.029

Neutral

(source)

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

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over