NM_007163.4:c.2248G>A

Variant names:

• chr18-45672918-G-A
• rs1123617
• NM_007163.4:c.2248G>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.2248G>A​(p.Val750Ile) variant causes a missense change. The variant allele was found at a frequency of 0.154 in 1,613,224 control chromosomes in the GnomAD database, including 20,173 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. V750A) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.14 (1633 hom., cov: 32)
  • Exomes 𝑓: 0.16 (18540 hom.)
• Consequence: SLC14A2 NM_007163.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.01
• Publications: 29 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 (MetaRNN=0.0036180615).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.283 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC14A2	NM_007163.4	c.2248G>A	p.Val750Ile	missense_variant	Exon 17 of 20	ENST00000255226.11	NP_009094.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC14A2	ENST00000255226.11	c.2248G>A	p.Val750Ile	missense_variant	Exon 17 of 20	1	NM_007163.4	ENSP00000255226.5

Frequencies

GnomAD3 genomes AF: 0.140 AC: 21251 AN: 152076 Hom.: 1628 Cov.: 32

Gnomad AFR AF: 0.0842

Gnomad AMI AF: 0.191

Gnomad AMR AF: 0.167

Gnomad ASJ AF: 0.156

Gnomad EAS AF: 0.295

Gnomad SAS AF: 0.186

Gnomad FIN AF: 0.131

Gnomad MID AF: 0.171

Gnomad NFE AF: 0.152

Gnomad OTH AF: 0.130

GnomAD2 exomes AF: 0.166 AC: 41508 AN: 250678 AF XY: 0.167

Gnomad AFR exome AF: 0.0853

Gnomad AMR exome AF: 0.180

Gnomad ASJ exome AF: 0.166

Gnomad EAS exome AF: 0.284

Gnomad FIN exome AF: 0.137

Gnomad NFE exome AF: 0.151

Gnomad OTH exome AF: 0.172

GnomAD4 exome AF: 0.156 AC: 227942 AN: 1461030 Hom.: 18540 Cov.: 33 AF XY: 0.157 AC XY: 114242 AN XY: 726822

African (AFR) AF: 0.0789 AC: 2642 AN: 33466

American (AMR) AF: 0.179 AC: 7968 AN: 44622

Ashkenazi Jewish (ASJ) AF: 0.164 AC: 4292 AN: 26110

East Asian (EAS) AF: 0.253 AC: 10027 AN: 39678

South Asian (SAS) AF: 0.192 AC: 16585 AN: 86162

European-Finnish (FIN) AF: 0.134 AC: 7137 AN: 53402

Middle Eastern (MID) AF: 0.182 AC: 1050 AN: 5766

European-Non Finnish (NFE) AF: 0.152 AC: 168437 AN: 1111454

Other (OTH) AF: 0.162 AC: 9804 AN: 60370

GnomAD4 genome AF: 0.140 AC: 21278 AN: 152194 Hom.: 1633 Cov.: 32 AF XY: 0.141 AC XY: 10484 AN XY: 74404

African (AFR) AF: 0.0843 AC: 3500 AN: 41540

American (AMR) AF: 0.168 AC: 2568 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.156 AC: 541 AN: 3470

East Asian (EAS) AF: 0.296 AC: 1529 AN: 5174

South Asian (SAS) AF: 0.187 AC: 899 AN: 4812

European-Finnish (FIN) AF: 0.131 AC: 1386 AN: 10594

Middle Eastern (MID) AF: 0.163 AC: 48 AN: 294

European-Non Finnish (NFE) AF: 0.152 AC: 10355 AN: 67988

Other (OTH) AF: 0.132 AC: 278 AN: 2112

Alfa AF: 0.149 Hom.: 8977

Bravo AF: 0.139

TwinsUK AF: 0.152 AC: 565

ALSPAC AF: 0.156 AC: 602

ESP6500AA AF: 0.0876 AC: 386

ESP6500EA AF: 0.152 AC: 1305

ExAC AF: 0.165 AC: 19991

Asia WGS AF: 0.226 AC: 787 AN: 3478

EpiCase AF: 0.148

EpiControl AF: 0.157

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.61	T
BayesDel_noAF	Benign	-0.51
CADD	Benign	19
DANN	Uncertain	0.99
DEOGEN2	Benign	0.20	T;T
Eigen	Benign	0.11
Eigen_PC	Benign	0.12
FATHMM_MKL	Uncertain	0.95	D
MetaRNN	Benign	0.0036	T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.5	L;L
PhyloP100		4.0
PrimateAI	Benign	0.33	T
PROVEAN	Benign	-0.55	.;N
REVEL	Benign	0.090
Sift	Benign	0.099	.;T
Sift4G	Benign	0.23	T;T
Polyphen		0.89	P;P
Vest4		0.077
MPC		0.078
ClinPred		0.030	T
GERP RS		4.0
Varity_R		0.052
gMVP		0.79
Mutation Taster		=96/4	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.10		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: rs1123617; hg19: chr18-43252883; COSMIC: COSV54907890;