rs2281819

Variant names:

• chr6-33803896-T-A
• rs2281819
• NM_002418.3:c.-8+57A>T

Your query was ambiguous. Multiple possible variants found:

• chr6-33803896-T-A
• chr6-33803896-T-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0680

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]

ACMG classification

Verdict is Benign. Variant got -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	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MLN	NM_002418.3	c.-8+57A>T		intron_variant	Intron 1 of 4	ENST00000430124.7	NP_002409.1
MLN	NM_001040109.2	c.-8+57A>T		intron_variant	Intron 1 of 4		NP_001035198.1
MLN	NM_001184698.2	c.-8+57A>T		intron_variant	Intron 1 of 4		NP_001171627.1

Ensembl

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

Frequencies

GnomAD3 genomes AF: 0.226 AC: 34330 AN: 152060 Hom.: 4124 Cov.: 32

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: 33 AN: 202 Hom.: 4 AF XY: 0.134 AC XY: 18 AN XY: 134

Gnomad4 AFR exome AF: 0.125

Gnomad4 AMR exome AF: 0.500

Gnomad4 ASJ exome AF: 0.500

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.167

Gnomad4 NFE exome AF: 0.173

Gnomad4 OTH exome AF: 0.143

GnomAD4 genome AF: 0.226 AC: 34346 AN: 152178 Hom.: 4131 Cov.: 32 AF XY: 0.233 AC XY: 17370 AN XY: 74408

Gnomad4 AFR AF: 0.176

Gnomad4 AMR AF: 0.324

Gnomad4 ASJ AF: 0.244

Gnomad4 EAS AF: 0.163

Gnomad4 SAS AF: 0.214

Gnomad4 FIN AF: 0.308

Gnomad4 NFE AF: 0.227

Gnomad4 OTH AF: 0.195

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
DANN	Benign	0.60

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: rs2281819; hg19: chr6-33771673;