rs2274459

Variant names:

• chr6-33794465-G-A
• rs2274459
• XR_926707.3:n.3778+1310G>A

Variant summary

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

The XR_926707.3(LOC105375024):​n.3778+1310G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.121 in 152,074 control chromosomes in the GnomAD database, including 1,457 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 0.12 (1457 hom., cov: 32)
• Consequence: LOC105375024 XR_926707.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0140
• Publications: 19 publications found

Genes affected

LOC105375024 (HGNC:):

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

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.172 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000430124.7. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MLN	NM_002418.3	MANE Select	c.*360C>T		downstream_gene	N/A	NP_002409.1	P12872-1
	MLN	NM_001040109.2		c.*360C>T		downstream_gene	N/A	NP_001035198.1	P12872-3
	MLN	NM_001184698.2		c.*360C>T		downstream_gene	N/A	NP_001171627.1	P12872-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MLN	ENST00000430124.7	TSL:1 MANE Select	c.*360C>T		downstream_gene	N/A	ENSP00000388825.2	P12872-1
	MLN	ENST00000960632.1		c.*360C>T		downstream_gene	N/A	ENSP00000630691.1
	MLN	ENST00000266003.9	TSL:5	c.*360C>T		downstream_gene	N/A	ENSP00000266003.5	P12872-3

Frequencies

GnomAD3 genomes AF: 0.121 AC: 18343 AN: 151956 Hom.: 1456 Cov.: 32

Gnomad AFR AF: 0.0323

Gnomad AMI AF: 0.125

Gnomad AMR AF: 0.144

Gnomad ASJ AF: 0.174

Gnomad EAS AF: 0.0466

Gnomad SAS AF: 0.0623

Gnomad FIN AF: 0.123

Gnomad MID AF: 0.212

Gnomad NFE AF: 0.175

Gnomad OTH AF: 0.152

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

GnomAD4 genome AF: 0.121 AC: 18349 AN: 152074 Hom.: 1457 Cov.: 32 AF XY: 0.116 AC XY: 8638 AN XY: 74342

African (AFR) AF: 0.0322 AC: 1338 AN: 41494

American (AMR) AF: 0.145 AC: 2207 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.174 AC: 601 AN: 3462

East Asian (EAS) AF: 0.0465 AC: 241 AN: 5178

South Asian (SAS) AF: 0.0625 AC: 301 AN: 4814

European-Finnish (FIN) AF: 0.123 AC: 1299 AN: 10574

Middle Eastern (MID) AF: 0.221 AC: 65 AN: 294

European-Non Finnish (NFE) AF: 0.175 AC: 11866 AN: 67964

Other (OTH) AF: 0.150 AC: 317 AN: 2114

Alfa AF: 0.153 Hom.: 4758

Bravo AF: 0.122

Asia WGS AF: 0.0600 AC: 208 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	12
DANN	Benign	0.60
PhyloP100		0.014

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs2274459; hg19: chr6-33762242;