chr12-8822219-T-C

Variant names:

• chr12-8822219-T-C
• rs11047432
• ENST00000537288.1:n.286+8443A>G

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The ENST00000537288.1(A2ML1-AS1):​n.286+8443A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.325 in 152,006 control chromosomes in the GnomAD database, including 8,488 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.32 (8488 hom., cov: 32)
• Consequence: A2ML1-AS1 ENST00000537288.1 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.712

Genes affected

A2ML1-AS1 (HGNC:41022): (A2ML1 antisense RNA 1)

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BP6: Variant 12-8822219-T-C is Benign according to our data. Variant chr12-8822219-T-C is described in ClinVar as [Benign]. Clinvar id is 561801.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.476 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
A2ML1-AS1	NR_046715.1	n.645+8443A>G		intron_variant	Intron 1 of 1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
A2ML1-AS1	ENST00000537288.1	n.286+8443A>G		intron_variant	Intron 1 of 1	3

Frequencies

GnomAD3 genomes AF: 0.325 AC: 49303 AN: 151888 Hom.: 8479 Cov.: 32

Gnomad AFR AF: 0.387

Gnomad AMI AF: 0.296

Gnomad AMR AF: 0.286

Gnomad ASJ AF: 0.218

Gnomad EAS AF: 0.467

Gnomad SAS AF: 0.493

Gnomad FIN AF: 0.368

Gnomad MID AF: 0.182

Gnomad NFE AF: 0.275

Gnomad OTH AF: 0.262

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

GnomAD4 genome AF: 0.325 AC: 49339 AN: 152006 Hom.: 8488 Cov.: 32 AF XY: 0.330 AC XY: 24504 AN XY: 74306

Gnomad4 AFR AF: 0.386

Gnomad4 AMR AF: 0.286

Gnomad4 ASJ AF: 0.218

Gnomad4 EAS AF: 0.467

Gnomad4 SAS AF: 0.492

Gnomad4 FIN AF: 0.368

Gnomad4 NFE AF: 0.275

Gnomad4 OTH AF: 0.265

Alfa AF: 0.286 Hom.: 582

Bravo AF: 0.319

Asia WGS AF: 0.430 AC: 1493 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Jun 14, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	6.8
DANN	Benign	0.74

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs11047432; hg19: chr12-8974815; COSMIC: COSV55299211;