6-33796256-C-T

Position:

• chr6-33796256-C-T

Variant summary

Our verdict is Benign. Variant got -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

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

Verdict is Benign. Variant got -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/exons	MANE	Protein	UniProt
MLN	NM_002418.3	c.235-651G>A		intron_variant		ENST00000430124.7	NP_002409.1
MLN	NM_001040109.2	c.235-651G>A		intron_variant			NP_001035198.1
MLN	NM_001184698.2	c.235-651G>A		intron_variant			NP_001171627.1
LOC105375024	XR_926707.3	n.3778+3101C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MLN	ENST00000430124.7	c.235-651G>A		intron_variant		1	NM_002418.3	ENSP00000388825.2
MLN	ENST00000507738.1	c.235-651G>A		intron_variant		1		ENSP00000425467.1
MLN	ENST00000266003.9	c.235-651G>A		intron_variant		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

Gnomad4 AFR AF: 0.315

Gnomad4 AMR AF: 0.350

Gnomad4 ASJ AF: 0.370

Gnomad4 EAS AF: 0.770

Gnomad4 SAS AF: 0.595

Gnomad4 FIN AF: 0.414

Gnomad4 NFE AF: 0.372

Gnomad4 OTH AF: 0.372

Alfa AF: 0.365 Hom.: 1298

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

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

LitVar

Other links and lift over

dbSNP: rs751728; hg19: chr6-33764033;