rs4894708

chr3-175295775-C-Achr3-175295775-C-G

Variant summary

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

The NM_207015.3(NAALADL2):c.940-28400C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.46 in 150,630 control chromosomes in the GnomAD database, including 16,696 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 0.46 (16696 hom., cov: 28)
• Consequence: NAALADL2 NM_207015.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.269

Genes affected

NAALADL2 (HGNC:23219): (N-acetylated alpha-linked acidic dipeptidase like 2) Predicted to enable metalloexopeptidase activity. Predicted to be involved in proteolysis. Predicted to act upstream of or within response to bacterium. Located in nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.98).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.521 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NAALADL2	NM_207015.3	c.940-28400C>A		intron_variant		ENST00000454872.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NAALADL2	ENST00000454872.6	c.940-28400C>A		intron_variant		1	NM_207015.3	P1
NAALADL2	ENST00000414826.1	c.120+39245C>A		intron_variant, NMD_transcript_variant		1
NAALADL2	ENST00000473253.5	n.1172-28400C>A		intron_variant, non_coding_transcript_variant		2
NAALADL2	ENST00000489299.5	n.679-28400C>A		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.460 AC: 69211 AN: 150508 Hom.: 16681 Cov.: 28

Gnomad AFR AF: 0.324

Gnomad AMI AF: 0.391

Gnomad AMR AF: 0.447

Gnomad ASJ AF: 0.465

Gnomad EAS AF: 0.413

Gnomad SAS AF: 0.505

Gnomad FIN AF: 0.593

Gnomad MID AF: 0.436

Gnomad NFE AF: 0.526

Gnomad OTH AF: 0.448

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

GnomAD4 genome AF: 0.460 AC: 69249 AN: 150630 Hom.: 16696 Cov.: 28 AF XY: 0.462 AC XY: 33919 AN XY: 73454

Gnomad4 AFR AF: 0.324

Gnomad4 AMR AF: 0.448

Gnomad4 ASJ AF: 0.465

Gnomad4 EAS AF: 0.413

Gnomad4 SAS AF: 0.505

Gnomad4 FIN AF: 0.593

Gnomad4 NFE AF: 0.526

Gnomad4 OTH AF: 0.449

Alfa AF: 0.477 Hom.: 3357

Bravo AF: 0.446

Asia WGS AF: 0.484 AC: 1682 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
Cadd	Benign	1.9
Dann	Benign	0.42

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: rs4894708; hg19: chr3-175013564;