7-30744935-C-T

Variant names:

• chr7-30744935-C-T
• rs10263500
• ENST00000484180.1:n.247-348C>T

Variant summary

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

The ENST00000484180.1(INMT):​n.247-348C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.436 in 152,134 control chromosomes in the GnomAD database, including 16,421 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 0.44 (16421 hom., cov: 34)
• Consequence: INMT ENST00000484180.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0240
• Publications: 1 publications found

Genes affected

INMT (HGNC:6069): (indolethylamine N-methyltransferase) N-methylation of endogenous and xenobiotic compounds is a major method by which they are degraded. This gene encodes an enzyme that N-methylates indoles such as tryptamine. Alternative splicing results in multiple transcript variants. Read-through transcription also exists between this gene and the downstream MINDY4 (aka FAM188B) gene. In rodents and other mammals such as cetartiodactyla this gene is in the opposite orientation compared to its orientation in human and other primates and this gene appears to have been lost in carnivora and chiroptera. [provided by RefSeq, Jul 2019]

LOC105375220 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.942 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LOC105375220	XR_001745154.2	n.603-348C>T		intron_variant	Intron 2 of 2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
INMT	ENST00000484180.1	n.247-348C>T		intron_variant	Intron 1 of 3	1

Frequencies

GnomAD3 genomes AF: 0.436 AC: 66263 AN: 152018 Hom.: 16416 Cov.: 34

Gnomad AFR AF: 0.226

Gnomad AMI AF: 0.560

Gnomad AMR AF: 0.537

Gnomad ASJ AF: 0.465

Gnomad EAS AF: 0.964

Gnomad SAS AF: 0.646

Gnomad FIN AF: 0.483

Gnomad MID AF: 0.462

Gnomad NFE AF: 0.474

Gnomad OTH AF: 0.486

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

GnomAD4 genome AF: 0.436 AC: 66293 AN: 152134 Hom.: 16421 Cov.: 34 AF XY: 0.445 AC XY: 33081 AN XY: 74354

African (AFR) AF: 0.226 AC: 9378 AN: 41508

American (AMR) AF: 0.537 AC: 8213 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.465 AC: 1615 AN: 3470

East Asian (EAS) AF: 0.964 AC: 4979 AN: 5164

South Asian (SAS) AF: 0.646 AC: 3113 AN: 4820

European-Finnish (FIN) AF: 0.483 AC: 5114 AN: 10584

Middle Eastern (MID) AF: 0.449 AC: 132 AN: 294

European-Non Finnish (NFE) AF: 0.474 AC: 32200 AN: 67982

Other (OTH) AF: 0.491 AC: 1038 AN: 2112

Alfa AF: 0.435 Hom.: 1884

Bravo AF: 0.433

Asia WGS AF: 0.753 AC: 2616 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	3.7
DANN	Benign	0.70
PhyloP100		-0.024

Splicing

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

Other links and lift over

dbSNP: rs10263500; hg19: chr7-30784551;