rs11018874

Variant names:

• chr11-90142269-G-A
• rs11018874
• NM_005467.4:c.195-5061G>A

Variant summary

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

The NM_005467.4(NAALAD2):​c.195-5061G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.1 in 152,026 control chromosomes in the GnomAD database, including 1,288 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 0.10 (1288 hom., cov: 32)
• Consequence: NAALAD2 NM_005467.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.230
• Publications: 13 publications found

Genes affected

NAALAD2 (HGNC:14526): (N-acetylated alpha-linked acidic dipeptidase 2) This gene is a member of the N-acetylated alpha-linked acidic dipeptidase (NAALADase) gene family. The representative member of this family is the gene encoding human prostate-specific membrane antigen (PSM), which is a marker of prostatic carcinomas and is the first to be shown to possess NAALADase activity. NAALADase cleaves N-acetyl-L-aspartate-L-glutamate (NAAG), which is a neuropeptide expressed both in the central nervous systems and in the periphery and is thought to function as a neurotransmitter. The product of this gene is a type II integral membrane protein. Transient transfection of this gene confers both NAALADase and dipetidyl peptidase IV activities to mammalian cells. This gene is highly expressed in ovary and testis as well as within discrete brain areas. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2014]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.258 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005467.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NAALAD2	NM_005467.4	MANE Select	c.195-5061G>A		intron	N/A	NP_005458.1	Q9Y3Q0-1
	NAALAD2	NM_001300930.2		c.195-5061G>A		intron	N/A	NP_001287859.1	J3KNJ3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NAALAD2	ENST00000534061.6	TSL:1 MANE Select	c.195-5061G>A		intron	N/A	ENSP00000432481.1	Q9Y3Q0-1
	NAALAD2	ENST00000375944.7	TSL:1	c.195-5061G>A		intron	N/A	ENSP00000365111.3	Q9Y3Q0-2
	NAALAD2	ENST00000524501.1	TSL:1	n.255-5061G>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.100 AC: 15260 AN: 151908 Hom.: 1280 Cov.: 32

Gnomad AFR AF: 0.0214

Gnomad AMI AF: 0.0484

Gnomad AMR AF: 0.264

Gnomad ASJ AF: 0.0524

Gnomad EAS AF: 0.246

Gnomad SAS AF: 0.103

Gnomad FIN AF: 0.168

Gnomad MID AF: 0.0759

Gnomad NFE AF: 0.0935

Gnomad OTH AF: 0.0954

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

GnomAD4 genome AF: 0.100 AC: 15273 AN: 152026 Hom.: 1288 Cov.: 32 AF XY: 0.108 AC XY: 8038 AN XY: 74326

African (AFR) AF: 0.0213 AC: 885 AN: 41494

American (AMR) AF: 0.265 AC: 4046 AN: 15250

Ashkenazi Jewish (ASJ) AF: 0.0524 AC: 182 AN: 3470

East Asian (EAS) AF: 0.245 AC: 1264 AN: 5164

South Asian (SAS) AF: 0.103 AC: 498 AN: 4814

European-Finnish (FIN) AF: 0.168 AC: 1778 AN: 10564

Middle Eastern (MID) AF: 0.0714 AC: 21 AN: 294

European-Non Finnish (NFE) AF: 0.0935 AC: 6357 AN: 67958

Other (OTH) AF: 0.0939 AC: 198 AN: 2108

Alfa AF: 0.0986 Hom.: 3305

Bravo AF: 0.107

Asia WGS AF: 0.142 AC: 496 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	2.1
DANN	Benign	0.47
PhyloP100		0.23
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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs11018874;

hg19: chr11-89875437;