rs3745009

chr18-45682394-G-Achr18-45682394-G-C

Variant summary

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

The NM_007163.4(SLC14A2):c.2638G>A(p.Ala880Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.443 in 1,613,370 control chromosomes in the GnomAD database, including 159,508 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 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 0.43 (14034 hom., cov: 31)
  • Exomes 𝑓: 0.44 (145474 hom.)
• Consequence: SLC14A2 NM_007163.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.09

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 (MetaRNN=0.0030146837).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.478 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLC14A2	NM_007163.4	c.2638G>A	p.Ala880Thr	missense_variant	20/20	ENST00000255226.11
LOC105372093	XR_935423.3	n.872+10001C>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC14A2	ENST00000255226.11	c.2638G>A	p.Ala880Thr	missense_variant	20/20	1	NM_007163.4	P1
	ENST00000589510.5	n.206+10001C>T		intron_variant, non_coding_transcript_variant		5
SLC14A2	ENST00000586448.5	c.2638G>A	p.Ala880Thr	missense_variant	21/21	2		P1

Frequencies

GnomAD3 genomes AF: 0.426 AC: 64683 AN: 151712 Hom.: 14026 Cov.: 31

Gnomad AFR AF: 0.380

Gnomad AMI AF: 0.461

Gnomad AMR AF: 0.404

Gnomad ASJ AF: 0.489

Gnomad EAS AF: 0.398

Gnomad SAS AF: 0.493

Gnomad FIN AF: 0.442

Gnomad MID AF: 0.437

Gnomad NFE AF: 0.451

Gnomad OTH AF: 0.435

GnomAD3 exomes AF: 0.436 AC: 109677 AN: 251386 Hom.: 24384 AF XY: 0.442 AC XY: 59986 AN XY: 135864

Gnomad AFR exome AF: 0.384

Gnomad AMR exome AF: 0.372

Gnomad ASJ exome AF: 0.487

Gnomad EAS exome AF: 0.407

Gnomad SAS exome AF: 0.499

Gnomad FIN exome AF: 0.445

Gnomad NFE exome AF: 0.445

Gnomad OTH exome AF: 0.436

GnomAD4 exome AF: 0.445 AC: 650075 AN: 1461540 Hom.: 145474 Cov.: 46 AF XY: 0.447 AC XY: 325110 AN XY: 727118

Gnomad4 AFR exome AF: 0.381

Gnomad4 AMR exome AF: 0.377

Gnomad4 ASJ exome AF: 0.488

Gnomad4 EAS exome AF: 0.401

Gnomad4 SAS exome AF: 0.493

Gnomad4 FIN exome AF: 0.442

Gnomad4 NFE exome AF: 0.446

Gnomad4 OTH exome AF: 0.448

GnomAD4 genome AF: 0.426 AC: 64727 AN: 151830 Hom.: 14034 Cov.: 31 AF XY: 0.428 AC XY: 31749 AN XY: 74166

Gnomad4 AFR AF: 0.380

Gnomad4 AMR AF: 0.403

Gnomad4 ASJ AF: 0.489

Gnomad4 EAS AF: 0.398

Gnomad4 SAS AF: 0.494

Gnomad4 FIN AF: 0.442

Gnomad4 NFE AF: 0.451

Gnomad4 OTH AF: 0.432

Alfa AF: 0.443 Hom.: 18151

Bravo AF: 0.418

TwinsUK AF: 0.451 AC: 1671

ALSPAC AF: 0.443 AC: 1707

ESP6500AA AF: 0.390 AC: 1720

ESP6500EA AF: 0.450 AC: 3870

ExAC AF: 0.436 AC: 52950

Asia WGS AF: 0.432 AC: 1499 AN: 3478

EpiCase AF: 0.456

EpiControl AF: 0.444

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.095
BayesDel_addAF	Benign	-0.62	T
BayesDel_noAF	Benign	-0.53
Cadd	Benign	19
Dann	Uncertain	0.99
DEOGEN2	Benign	0.25	T;T
Eigen	Benign	-0.097
Eigen_PC	Benign	0.071
FATHMM_MKL	Uncertain	0.87	D
MetaRNN	Benign	0.0030	T;T
MetaSVM	Benign	-0.94	T
MutationAssessor	Uncertain	2.1	M;M
MutationTaster	Benign	0.50	P;P;P
PrimateAI	Benign	0.41	T
Sift4G	Benign	0.34	T;T
Polyphen		0.017	B;B
Vest4		0.059
MPC		0.081
ClinPred		0.016	T
GERP RS		5.1
Varity_R		0.092
gMVP		0.83

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: rs3745009; hg19: chr18-43262359; COSMIC: COSV54906325; COSMIC: COSV54906325;