rs11680305

Positions:

• chr2-3504360-A-G
• chr2-3504360-A-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_018269.4(ADI1):​c.241-3367T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.502 in 152,136 control chromosomes in the GnomAD database, including 22,469 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 0.50 (22469 hom., cov: 33)
• Consequence: ADI1 NM_018269.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0340

Genes affected

ADI1 (HGNC:30576): (acireductone dioxygenase 1) This gene encodes an enzyme that belongs to the aci-reductone dioxygenase family of metal-binding enzymes, which are involved in methionine salvage. This enzyme may regulate mRNA processing in the nucleus, and may carry out different functions depending on its localization. Related pseudogenes have been defined on chromosomes 8 and 20. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Apr 2015]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.99).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.825 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ADI1	NM_018269.4	c.241-3367T>C		intron_variant		ENST00000327435.11
ADI1	NM_001306077.2	c.223-3367T>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ADI1	ENST00000327435.11	c.241-3367T>C		intron_variant		1	NM_018269.4	P1
ADI1	ENST00000382093.5	c.223-3367T>C		intron_variant		2

Frequencies

GnomAD3 genomes AF: 0.502 AC: 76330 AN: 152018 Hom.: 22423 Cov.: 33

Gnomad AFR AF: 0.832

Gnomad AMI AF: 0.429

Gnomad AMR AF: 0.414

Gnomad ASJ AF: 0.430

Gnomad EAS AF: 0.452

Gnomad SAS AF: 0.420

Gnomad FIN AF: 0.361

Gnomad MID AF: 0.459

Gnomad NFE AF: 0.358

Gnomad OTH AF: 0.492

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

GnomAD4 genome AF: 0.502 AC: 76427 AN: 152136 Hom.: 22469 Cov.: 33 AF XY: 0.498 AC XY: 37070 AN XY: 74378

Gnomad4 AFR AF: 0.832

Gnomad4 AMR AF: 0.413

Gnomad4 ASJ AF: 0.430

Gnomad4 EAS AF: 0.452

Gnomad4 SAS AF: 0.419

Gnomad4 FIN AF: 0.361

Gnomad4 NFE AF: 0.358

Gnomad4 OTH AF: 0.488

Alfa AF: 0.383 Hom.: 13484

Bravo AF: 0.524

Asia WGS AF: 0.460 AC: 1598 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	3.4
DANN	Benign	0.37

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

Publications

LitVar

Other links and lift over

dbSNP: rs11680305; hg19: chr2-3508131;