18-45682546-T-C

Variant names:

• chr18-45682546-T-C
• rs16978449
• NM_007163.4:c.*27T>C

Variant summary

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

The NM_007163.4(SLC14A2):​c.*27T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00498 in 1,590,968 control chromosomes in the GnomAD database, including 330 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 0.026 (156 hom., cov: 32)
  • Exomes 𝑓: 0.0027 (174 hom.)
• Consequence: SLC14A2 NM_007163.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.574
• Publications: 1 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]

ENSG00000288545 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0884 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC14A2	NM_007163.4	MANE Select	c.*27T>C		3_prime_UTR	Exon 20 of 20	NP_009094.3
	SLC14A2	NM_001242692.2		c.*27T>C		3_prime_UTR	Exon 21 of 21	NP_001229621.1
	SLC14A2	NM_001371319.1		c.*27T>C		3_prime_UTR	Exon 24 of 24	NP_001358248.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC14A2	ENST00000255226.11	TSL:1 MANE Select	c.*27T>C		3_prime_UTR	Exon 20 of 20	ENSP00000255226.5
	SLC14A2	ENST00000586448.5	TSL:2	c.*27T>C		3_prime_UTR	Exon 21 of 21	ENSP00000465953.1
	ENSG00000288545	ENST00000589510.5	TSL:5	n.206+9849A>G		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.0261 AC: 3968 AN: 152150 Hom.: 155 Cov.: 32

Gnomad AFR AF: 0.0907

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00988

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000623

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0127

Gnomad NFE AF: 0.000235

Gnomad OTH AF: 0.0177

GnomAD2 exomes AF: 0.00670 AC: 1683 AN: 251262 AF XY: 0.00472

Gnomad AFR exome AF: 0.0903

Gnomad AMR exome AF: 0.00500

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000176

Gnomad OTH exome AF: 0.00229

GnomAD4 exome AF: 0.00274 AC: 3938 AN: 1438700 Hom.: 174 Cov.: 26 AF XY: 0.00236 AC XY: 1690 AN XY: 717336

African (AFR) AF: 0.0971 AC: 3207 AN: 33032

American (AMR) AF: 0.00530 AC: 237 AN: 44708

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25988

East Asian (EAS) AF: 0.00 AC: 0 AN: 39610

South Asian (SAS) AF: 0.000315 AC: 27 AN: 85778

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53412

Middle Eastern (MID) AF: 0.00401 AC: 23 AN: 5730

European-Non Finnish (NFE) AF: 0.0000642 AC: 70 AN: 1090860

Other (OTH) AF: 0.00628 AC: 374 AN: 59582

GnomAD4 genome AF: 0.0262 AC: 3982 AN: 152268 Hom.: 156 Cov.: 32 AF XY: 0.0258 AC XY: 1923 AN XY: 74448

African (AFR) AF: 0.0908 AC: 3771 AN: 41542

American (AMR) AF: 0.00987 AC: 151 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5186

South Asian (SAS) AF: 0.000623 AC: 3 AN: 4814

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10612

Middle Eastern (MID) AF: 0.0136 AC: 4 AN: 294

European-Non Finnish (NFE) AF: 0.000235 AC: 16 AN: 68018

Other (OTH) AF: 0.0175 AC: 37 AN: 2114

Alfa AF: 0.0130 Hom.: 24

Bravo AF: 0.0307

Asia WGS AF: 0.00577 AC: 20 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	1.2
DANN	Benign	0.49
PhyloP100		-0.57
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: rs16978449; hg19: chr18-43262511;