18-45630229-G-A

Variant names:

• chr18-45630229-G-A
• rs1484874
• NM_007163.4:c.522-2121G>A

Variant summary

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

The NM_007163.4(SLC14A2):​c.522-2121G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.367 in 152,014 control chromosomes in the GnomAD database, including 10,520 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 0.37 (10520 hom., cov: 32)
• Consequence: SLC14A2 NM_007163.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.117
• Publications: 8 publications found

Genes affected

SLC14A2 (HGNC:10919): (solute carrier family 14 member 2) The protein encoded by this gene belongs to the urea transporter family. In mammalian cells, urea is the chief end product of nitrogen catabolism, and plays an important role in the urinary concentration mechanism. This protein is expressed in the inner medulla of the kidney, and mediates rapid transepithelial urea transport across the inner medullary collecting duct. Alternatively spliced transcript variants have been found for this gene. [provided by RefSeq, Sep 2011]

ENSG00000287943 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.96).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.407 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_007163.4. 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
	SLC14A2	NM_007163.4	MANE Select	c.522-2121G>A		intron	N/A	NP_009094.3
	SLC14A2	NM_001242692.2		c.522-2121G>A		intron	N/A	NP_001229621.1	Q15849-1
	SLC14A2	NM_001371319.1		c.522-2121G>A		intron	N/A	NP_001358248.1	Q15849-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC14A2	ENST00000255226.11	TSL:1 MANE Select	c.522-2121G>A		intron	N/A	ENSP00000255226.5	Q15849-1
	SLC14A2	ENST00000586448.5	TSL:2	c.522-2121G>A		intron	N/A	ENSP00000465953.1	Q15849-1
	SLC14A2	ENST00000323329.3	TSL:2	n.522-2121G>A		intron	N/A	ENSP00000320689.3	E7EPU1

Frequencies

GnomAD3 genomes AF: 0.367 AC: 55760 AN: 151896 Hom.: 10498 Cov.: 32

Gnomad AFR AF: 0.292

Gnomad AMI AF: 0.418

Gnomad AMR AF: 0.356

Gnomad ASJ AF: 0.530

Gnomad EAS AF: 0.396

Gnomad SAS AF: 0.303

Gnomad FIN AF: 0.343

Gnomad MID AF: 0.399

Gnomad NFE AF: 0.411

Gnomad OTH AF: 0.415

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

GnomAD4 genome AF: 0.367 AC: 55823 AN: 152014 Hom.: 10520 Cov.: 32 AF XY: 0.363 AC XY: 26940 AN XY: 74294

African (AFR) AF: 0.292 AC: 12104 AN: 41448

American (AMR) AF: 0.356 AC: 5441 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.530 AC: 1839 AN: 3470

East Asian (EAS) AF: 0.397 AC: 2050 AN: 5166

South Asian (SAS) AF: 0.304 AC: 1458 AN: 4802

European-Finnish (FIN) AF: 0.343 AC: 3619 AN: 10562

Middle Eastern (MID) AF: 0.408 AC: 120 AN: 294

European-Non Finnish (NFE) AF: 0.411 AC: 27937 AN: 67982

Other (OTH) AF: 0.414 AC: 875 AN: 2114

Alfa AF: 0.392 Hom.: 11121

Bravo AF: 0.367

Asia WGS AF: 0.332 AC: 1154 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	0.63
DANN	Benign	0.21
PhyloP100		-0.12
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: rs1484874; hg19: chr18-43210194;