Genetic Variant NM_002418.3: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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
MLN	NM_002418.3 link	c.-8+57A>T	intron_variant	Intron 1 of 4	ENST00000430124.7	NP_002409.1	P12872-1
MLN	NM_001040109.2 link	c.-8+57A>T	intron_variant	Intron 1 of 4		NP_001035198.1	P12872-3
MLN	NM_001184698.2 link	c.-8+57A>T	intron_variant	Intron 1 of 4		NP_001171627.1	P12872-2

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
MLN	ENST00000430124.7 link	c.-8+57A>T	intron_variant	Intron 1 of 4	1	NM_002418.3	ENSP00000388825.2	P12872-1
MLN	ENST00000507738.1 link	c.-8+57A>T	intron_variant	Intron 1 of 4	1		ENSP00000425467.1	P12872-2
MLN	ENST00000266003.9 link	c.-8+57A>T	intron_variant	Intron 1 of 4	5		ENSP00000266003.5	P12872-3

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 v4.3

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over