rs9960464

Positions:

• chr18-45666191-G-A

Variant summary

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

The NM_007163.4(SLC14A2):​c.1529G>A​(p.Arg510Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.446 in 1,611,038 control chromosomes in the GnomAD database, including 162,448 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

• Frequency:
  • Genomes: 𝑓 0.42 (13664 hom., cov: 31)
  • Exomes 𝑓: 0.45 (148784 hom.)
• Consequence: SLC14A2 NM_007163.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.755

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]

LOC105372093 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=1.6295353E-5).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.46 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLC14A2	NM_007163.4	c.1529G>A	p.Arg510Gln	missense_variant	12/20	ENST00000255226.11	NP_009094.3
LOC105372093	XR_935423.3	n.872+26204C>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLC14A2	ENST00000255226.11	c.1529G>A	p.Arg510Gln	missense_variant	12/20	1	NM_007163.4	ENSP00000255226	P1
SLC14A2	ENST00000586448.5	c.1529G>A	p.Arg510Gln	missense_variant	13/21	2		ENSP00000465953	P1

Frequencies

GnomAD3 genomes AF: 0.417 AC: 63300 AN: 151762 Hom.: 13665 Cov.: 31

Gnomad AFR AF: 0.324

Gnomad AMI AF: 0.276

Gnomad AMR AF: 0.470

Gnomad ASJ AF: 0.398

Gnomad EAS AF: 0.326

Gnomad SAS AF: 0.434

Gnomad FIN AF: 0.480

Gnomad MID AF: 0.427

Gnomad NFE AF: 0.461

Gnomad OTH AF: 0.401

GnomAD3 exomes AF: 0.447 AC: 112138 AN: 251106 Hom.: 25577 AF XY: 0.445 AC XY: 60457 AN XY: 135740

Gnomad AFR exome AF: 0.318

Gnomad AMR exome AF: 0.530

Gnomad ASJ exome AF: 0.387

Gnomad EAS exome AF: 0.324

Gnomad SAS exome AF: 0.439

Gnomad FIN exome AF: 0.488

Gnomad NFE exome AF: 0.459

Gnomad OTH exome AF: 0.448

GnomAD4 exome AF: 0.449 AC: 655602 AN: 1459156 Hom.: 148784 Cov.: 33 AF XY: 0.449 AC XY: 326175 AN XY: 726016

Gnomad4 AFR exome AF: 0.311

Gnomad4 AMR exome AF: 0.523

Gnomad4 ASJ exome AF: 0.383

Gnomad4 EAS exome AF: 0.350

Gnomad4 SAS exome AF: 0.445

Gnomad4 FIN exome AF: 0.491

Gnomad4 NFE exome AF: 0.455

Gnomad4 OTH exome AF: 0.432

GnomAD4 genome AF: 0.417 AC: 63312 AN: 151882 Hom.: 13664 Cov.: 31 AF XY: 0.417 AC XY: 30931 AN XY: 74226

Gnomad4 AFR AF: 0.323

Gnomad4 AMR AF: 0.469

Gnomad4 ASJ AF: 0.398

Gnomad4 EAS AF: 0.326

Gnomad4 SAS AF: 0.435

Gnomad4 FIN AF: 0.480

Gnomad4 NFE AF: 0.461

Gnomad4 OTH AF: 0.404

Alfa AF: 0.446 Hom.: 40052

Bravo AF: 0.407

TwinsUK AF: 0.455 AC: 1688

ALSPAC AF: 0.450 AC: 1734

ESP6500AA AF: 0.328 AC: 1446

ESP6500EA AF: 0.447 AC: 3848

ExAC AF: 0.442 AC: 53673

Asia WGS AF: 0.377 AC: 1314 AN: 3478

EpiCase AF: 0.456

EpiControl AF: 0.452

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.063
BayesDel_addAF	Benign	-0.84	T
BayesDel_noAF	Benign	-0.83
CADD	Benign	0.26
DANN	Benign	0.84
DEOGEN2	Benign	0.14	T;T
Eigen	Benign	-1.9
Eigen_PC	Benign	-1.9
FATHMM_MKL	Benign	0.0030	N
MetaRNN	Benign	0.000016	T;T
MetaSVM	Benign	-0.95	T
MutationAssessor	Benign	-1.9	N;N
MutationTaster	Benign	1.0	P;P;P
PrimateAI	Benign	0.22	T
PROVEAN	Benign	-0.12	.;N
REVEL	Benign	0.024
Sift	Benign	0.74	.;T
Sift4G	Benign	0.58	T;T
Polyphen		0.0	B;B
Vest4		0.019
MPC		0.074
ClinPred		0.028	T
GERP RS		-12
Varity_R		0.022
gMVP		0.32

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs9960464; hg19: chr18-43246156; COSMIC: COSV54907019; COSMIC: COSV54907019;