7-30703395-A-G

Variant names:

• chr7-30703395-A-G
• rs255125
• ENST00000484180.1:n.246+5165A>G

Variant summary

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

The ENST00000484180.1(INMT):​n.246+5165A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.619 in 151,992 control chromosomes in the GnomAD database, including 29,454 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 0.62 (29454 hom., cov: 32)
• Consequence: INMT ENST00000484180.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.901
• Publications: 8 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=-0.99).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.674 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LOC105375220	XR_001745154.2	n.489+5165A>G		intron_variant	Intron 1 of 2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
INMT	ENST00000484180.1	n.246+5165A>G		intron_variant	Intron 1 of 3	1

Frequencies

GnomAD3 genomes AF: 0.618 AC: 93925 AN: 151874 Hom.: 29418 Cov.: 32

Gnomad AFR AF: 0.529

Gnomad AMI AF: 0.698

Gnomad AMR AF: 0.546

Gnomad ASJ AF: 0.687

Gnomad EAS AF: 0.623

Gnomad SAS AF: 0.534

Gnomad FIN AF: 0.690

Gnomad MID AF: 0.670

Gnomad NFE AF: 0.679

Gnomad OTH AF: 0.618

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

GnomAD4 genome AF: 0.619 AC: 94013 AN: 151992 Hom.: 29454 Cov.: 32 AF XY: 0.619 AC XY: 45960 AN XY: 74292

African (AFR) AF: 0.530 AC: 21961 AN: 41442

American (AMR) AF: 0.546 AC: 8335 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.687 AC: 2385 AN: 3470

East Asian (EAS) AF: 0.623 AC: 3215 AN: 5162

South Asian (SAS) AF: 0.534 AC: 2574 AN: 4820

European-Finnish (FIN) AF: 0.690 AC: 7282 AN: 10546

Middle Eastern (MID) AF: 0.672 AC: 195 AN: 290

European-Non Finnish (NFE) AF: 0.679 AC: 46138 AN: 67968

Other (OTH) AF: 0.614 AC: 1294 AN: 2108

Alfa AF: 0.655 Hom.: 98766

Bravo AF: 0.604

Asia WGS AF: 0.566 AC: 1969 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	0.40
DANN	Benign	0.59
PhyloP100		-0.90

Splicing

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

Other links and lift over

dbSNP: rs255125; hg19: chr7-30743011;