rs9960464

Variant names:

• chr18-45666191-G-A
• rs9960464
• NM_007163.4:c.1529G>A

Your query was ambiguous. Multiple possible variants found:

• chr18-45666191-G-A
• chr18-45666191-G-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.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. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• 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
• Publications: 32 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 (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 rank	MANE	Protein	UniProt
SLC14A2	NM_007163.4	c.1529G>A	p.Arg510Gln	missense_variant	Exon 12 of 20	ENST00000255226.11	NP_009094.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC14A2	ENST00000255226.11	c.1529G>A	p.Arg510Gln	missense_variant	Exon 12 of 20	1	NM_007163.4	ENSP00000255226.5
SLC14A2	ENST00000586448.5	c.1529G>A	p.Arg510Gln	missense_variant	Exon 13 of 21	2		ENSP00000465953.1
ENSG00000287943	ENST00000729208.1	n.228+22558C>T		intron_variant	Intron 1 of 2
ENSG00000287943	ENST00000729209.1	n.228+22558C>T		intron_variant	Intron 1 of 3

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

GnomAD2 exomes AF: 0.447 AC: 112138 AN: 251106 AF XY: 0.445

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 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

African (AFR) AF: 0.311 AC: 10399 AN: 33402

American (AMR) AF: 0.523 AC: 23380 AN: 44708

Ashkenazi Jewish (ASJ) AF: 0.383 AC: 10008 AN: 26104

East Asian (EAS) AF: 0.350 AC: 13900 AN: 39678

South Asian (SAS) AF: 0.445 AC: 38377 AN: 86180

European-Finnish (FIN) AF: 0.491 AC: 26232 AN: 53398

Middle Eastern (MID) AF: 0.377 AC: 2170 AN: 5762

European-Non Finnish (NFE) AF: 0.455 AC: 505047 AN: 1109590

Other (OTH) AF: 0.432 AC: 26089 AN: 60334

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

African (AFR) AF: 0.323 AC: 13386 AN: 41400

American (AMR) AF: 0.469 AC: 7165 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.398 AC: 1377 AN: 3464

East Asian (EAS) AF: 0.326 AC: 1682 AN: 5154

South Asian (SAS) AF: 0.435 AC: 2092 AN: 4810

European-Finnish (FIN) AF: 0.480 AC: 5047 AN: 10520

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

European-Non Finnish (NFE) AF: 0.461 AC: 31340 AN: 67956

Other (OTH) AF: 0.404 AC: 852 AN: 2110

Alfa AF: 0.443 Hom.: 76271

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
PhyloP100		-0.76
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
Mutation Taster		=300/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs9960464; hg19: chr18-43246156; COSMIC: COSV54907019; COSMIC: COSV54907019;