rs16978449

Positions:

• chr18-45682546-T-C

Variant summary

Our verdict is Benign. Variant got -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

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]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLC14A2	NM_007163.4	c.*27T>C		3_prime_UTR_variant	20/20	ENST00000255226.11
LOC105372093	XR_935423.3	n.872+9849A>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC14A2	ENST00000255226.11	c.*27T>C		3_prime_UTR_variant	20/20	1	NM_007163.4	P1
	ENST00000589510.5	n.206+9849A>G		intron_variant, non_coding_transcript_variant		5
SLC14A2	ENST00000586448.5	c.*27T>C		3_prime_UTR_variant	21/21	2		P1

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

GnomAD3 exomes AF: 0.00670 AC: 1683 AN: 251262 Hom.: 75 AF XY: 0.00472 AC XY: 641 AN XY: 135796

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 SAS exome AF: 0.000261

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

Gnomad4 AFR exome AF: 0.0971

Gnomad4 AMR exome AF: 0.00530

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000315

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000642

Gnomad4 OTH exome AF: 0.00628

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

Gnomad4 AFR AF: 0.0908

Gnomad4 AMR AF: 0.00987

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000623

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000235

Gnomad4 OTH AF: 0.0175

Alfa AF: 0.0140 Hom.: 14

Bravo AF: 0.0307

Asia WGS AF: 0.00577 AC: 20 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	1.2
DANN	Benign	0.49

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: rs16978449; hg19: chr18-43262511;