rs2372216

Variant names:

• chr3-30791148-T-C
• rs2372216
• NM_207359.3:c.1251-4742A>G

Variant summary

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

The NM_207359.3(GADL1):​c.1251-4742A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.144 in 152,140 control chromosomes in the GnomAD database, including 4,130 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 0.14 (4130 hom., cov: 32)
• Consequence: GADL1 NM_207359.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0580
• Publications: 0 publications found

Genes affected

GADL1 (HGNC:27949): (glutamate decarboxylase like 1) Predicted to enable aspartate 1-decarboxylase activity; pyridoxal phosphate binding activity; and sulfinoalanine decarboxylase activity. Predicted to be involved in carboxylic acid metabolic process. Predicted to be located in cytosol. [provided by Alliance of Genome Resources, Apr 2022]

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 (AFR) allele frequency at 95% confidence interval = 0.419 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GADL1	NM_207359.3	c.1251-4742A>G		intron_variant	Intron 12 of 14	ENST00000282538.10	NP_997242.2
GADL1	XM_017006297.2	c.1194-4742A>G		intron_variant	Intron 12 of 14		XP_016861786.1
GADL1	XM_047448071.1	c.1251-4742A>G		intron_variant	Intron 12 of 13		XP_047304027.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GADL1	ENST00000282538.10	c.1251-4742A>G		intron_variant	Intron 12 of 14	5	NM_207359.3	ENSP00000282538.5

Frequencies

GnomAD3 genomes AF: 0.144 AC: 21824 AN: 152022 Hom.: 4115 Cov.: 32

Gnomad AFR AF: 0.424

Gnomad AMI AF: 0.00548

Gnomad AMR AF: 0.0585

Gnomad ASJ AF: 0.0133

Gnomad EAS AF: 0.328

Gnomad SAS AF: 0.0947

Gnomad FIN AF: 0.0187

Gnomad MID AF: 0.0633

Gnomad NFE AF: 0.0108

Gnomad OTH AF: 0.120

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

GnomAD4 genome AF: 0.144 AC: 21881 AN: 152140 Hom.: 4130 Cov.: 32 AF XY: 0.143 AC XY: 10675 AN XY: 74394

African (AFR) AF: 0.424 AC: 17572 AN: 41466

American (AMR) AF: 0.0583 AC: 891 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.0133 AC: 46 AN: 3470

East Asian (EAS) AF: 0.328 AC: 1698 AN: 5172

South Asian (SAS) AF: 0.0943 AC: 455 AN: 4824

European-Finnish (FIN) AF: 0.0187 AC: 199 AN: 10614

Middle Eastern (MID) AF: 0.0612 AC: 18 AN: 294

European-Non Finnish (NFE) AF: 0.0108 AC: 737 AN: 68008

Other (OTH) AF: 0.123 AC: 260 AN: 2110

Alfa AF: 0.0870 Hom.: 288

Bravo AF: 0.160

Asia WGS AF: 0.206 AC: 713 AN: 3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	3.1
DANN	Benign	0.74
PhyloP100		0.058
Mutation Taster		=100/0	polymorphism (auto)

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: rs2372216; hg19: chr3-30832640;