rs11191454

Variant names:

• chr10-102900247-A-G
• rs11191454
• NM_020682.4:c.1021-346A>G

Variant summary

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

The NM_020682.4(AS3MT):​c.1021-346A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0835 in 152,266 control chromosomes in the GnomAD database, including 806 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 0.083 (806 hom., cov: 32)
• Consequence: AS3MT NM_020682.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0230
• Publications: 67 publications found

Genes affected

AS3MT (HGNC:17452): (arsenite methyltransferase) AS3MT catalyzes the transfer of a methyl group from S-adenosyl-L-methionine (AdoMet) to trivalent arsenical and may play a role in arsenic metabolism (Lin et al., 2002 [PubMed 11790780]).[supplied by OMIM, Mar 2008]

BORCS7-ASMT (HGNC:49183): (BORCS7-ASMT readthrough (NMD candidate)) This locus represents naturally occurring read-through transcription between the neighboring C10orf32 (chromosome 10 open reading frame 32) and AS3MT (arsenic, +3 oxidation state, methyltransferase) genes. The read-through transcript is a candidate for nonsense-mediated mRNA decay (NMD), and is therefore unlikely to produce a protein product. [provided by RefSeq, Dec 2010]

ENSG00000286575 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.266 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
AS3MT	NM_020682.4	c.1021-346A>G		intron_variant	Intron 10 of 10	ENST00000369880.8	NP_065733.2
BORCS7-ASMT	NR_037644.1	n.1426-346A>G		intron_variant	Intron 14 of 14
LOC107984265	NR_160733.1	n.285+147T>C		intron_variant	Intron 2 of 2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
AS3MT	ENST00000369880.8	c.1021-346A>G		intron_variant	Intron 10 of 10	1	NM_020682.4	ENSP00000358896.3
BORCS7-ASMT	ENST00000299353.6	n.*1028-346A>G		intron_variant	Intron 14 of 14	5		ENSP00000299353.5

Frequencies

GnomAD3 genomes AF: 0.0835 AC: 12703 AN: 152148 Hom.: 803 Cov.: 32

Gnomad AFR AF: 0.0214

Gnomad AMI AF: 0.0175

Gnomad AMR AF: 0.134

Gnomad ASJ AF: 0.0697

Gnomad EAS AF: 0.277

Gnomad SAS AF: 0.184

Gnomad FIN AF: 0.0757

Gnomad MID AF: 0.0696

Gnomad NFE AF: 0.0906

Gnomad OTH AF: 0.0951

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

GnomAD4 genome AF: 0.0835 AC: 12712 AN: 152266 Hom.: 806 Cov.: 32 AF XY: 0.0860 AC XY: 6401 AN XY: 74438

African (AFR) AF: 0.0213 AC: 886 AN: 41564

American (AMR) AF: 0.134 AC: 2052 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.0697 AC: 242 AN: 3472

East Asian (EAS) AF: 0.278 AC: 1437 AN: 5178

South Asian (SAS) AF: 0.183 AC: 886 AN: 4832

European-Finnish (FIN) AF: 0.0757 AC: 803 AN: 10606

Middle Eastern (MID) AF: 0.0680 AC: 20 AN: 294

European-Non Finnish (NFE) AF: 0.0906 AC: 6162 AN: 68010

Other (OTH) AF: 0.0984 AC: 208 AN: 2114

Alfa AF: 0.0942 Hom.: 2707

Bravo AF: 0.0854

Asia WGS AF: 0.198 AC: 685 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	3.2
DANN	Benign	0.35
PhyloP100		-0.023

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

Other links and lift over

dbSNP: rs11191454; hg19: chr10-104660004;