6-33796256-C-T

Variant names:

• chr6-33796256-C-T
• rs751728
• NM_002418.3:c.235-651G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_002418.3(MLN):​c.235-651G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.378 in 152,010 control chromosomes in the GnomAD database, including 11,473 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 0.38 (11473 hom., cov: 31)
• Consequence: MLN NM_002418.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0550
• Publications: 17 publications found

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]

LOC105375024 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.72).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.75 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MLN	NM_002418.3	c.235-651G>A		intron_variant	Intron 3 of 4	ENST00000430124.7	NP_002409.1
MLN	NM_001040109.2	c.235-651G>A		intron_variant	Intron 3 of 4		NP_001035198.1
MLN	NM_001184698.2	c.235-651G>A		intron_variant	Intron 3 of 4		NP_001171627.1
LOC105375024	XR_926707.3	n.3778+3101C>T		intron_variant	Intron 1 of 2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MLN	ENST00000430124.7	c.235-651G>A		intron_variant	Intron 3 of 4	1	NM_002418.3	ENSP00000388825.2
MLN	ENST00000507738.1	c.235-651G>A		intron_variant	Intron 3 of 4	1		ENSP00000425467.1
MLN	ENST00000266003.9	c.235-651G>A		intron_variant	Intron 3 of 4	5		ENSP00000266003.5

Frequencies

GnomAD3 genomes AF: 0.379 AC: 57496 AN: 151892 Hom.: 11471 Cov.: 31

Gnomad AFR AF: 0.316

Gnomad AMI AF: 0.442

Gnomad AMR AF: 0.350

Gnomad ASJ AF: 0.370

Gnomad EAS AF: 0.769

Gnomad SAS AF: 0.595

Gnomad FIN AF: 0.414

Gnomad MID AF: 0.408

Gnomad NFE AF: 0.372

Gnomad OTH AF: 0.366

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.378 AC: 57514 AN: 152010 Hom.: 11473 Cov.: 31 AF XY: 0.383 AC XY: 28466 AN XY: 74298

African (AFR) AF: 0.315 AC: 13068 AN: 41436

American (AMR) AF: 0.350 AC: 5342 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.370 AC: 1284 AN: 3472

East Asian (EAS) AF: 0.770 AC: 3980 AN: 5172

South Asian (SAS) AF: 0.595 AC: 2869 AN: 4818

European-Finnish (FIN) AF: 0.414 AC: 4371 AN: 10552

Middle Eastern (MID) AF: 0.405 AC: 119 AN: 294

European-Non Finnish (NFE) AF: 0.372 AC: 25293 AN: 67974

Other (OTH) AF: 0.372 AC: 785 AN: 2108

Alfa AF: 0.380 Hom.: 18363

Bravo AF: 0.370

Asia WGS AF: 0.612 AC: 2131 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.72
CADD	Benign	9.2
DANN	Benign	0.83
PhyloP100		-0.055
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs751728; hg19: chr6-33764033;