18-45644160-G-A

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP6_Moderate BS2

The NM_007163.4(SLC14A2):c.1351G>A(p.Gly451Arg) variant causes a missense, splice region change. The variant allele was found at a frequency of 0.00074 in 1,614,086 control chromosomes in the GnomAD database, including 5 homozygotes. In-silico tool predicts a benign outcome for this variant. 2/3 splice prediction tools predicting alterations to normal splicing. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0035 (2 hom., cov: 32)
  • Exomes 𝑓: 0.00045 (3 hom.)
• Consequence: SLC14A2 NM_007163.4 missense, splice_region
• Scores: Splicing: ADA: 1.000
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 7.04

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 Likely_benign. Variant got -6 ACMG points.

• BP6: Variant 18-45644160-G-A is Benign according to our data. Variant chr18-45644160-G-A is described in ClinVar as [Benign]. Clinvar id is 784378.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High Homozygotes in GnomAd at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLC14A2	NM_007163.4	c.1351G>A	p.Gly451Arg	missense_variant, splice_region_variant	10/20	ENST00000255226.11
LOC105372093	XR_935423.3	n.873-7003C>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC14A2	ENST00000255226.11	c.1351G>A	p.Gly451Arg	missense_variant, splice_region_variant	10/20	1	NM_007163.4	P1
SLC14A2	ENST00000586448.5	c.1351G>A	p.Gly451Arg	missense_variant, splice_region_variant	11/21	2		P1
SLC14A2	ENST00000323329.3	c.*673G>A		3_prime_UTR_variant, NMD_transcript_variant	11/11	2

Frequencies

GnomAD3 genomes AF: 0.00351 AC: 534 AN: 152184 Hom.: 2 Cov.: 32

Gnomad AFR AF: 0.0121

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00164

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000294

Gnomad OTH AF: 0.00191

GnomAD3 exomes AF: 0.000972 AC: 244 AN: 251058 Hom.: 1 AF XY: 0.000840 AC XY: 114 AN XY: 135672

Gnomad AFR exome AF: 0.0127

Gnomad AMR exome AF: 0.000347

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000544

Gnomad SAS exome AF: 0.000131

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000167

Gnomad OTH exome AF: 0.000163

GnomAD4 exome AF: 0.000451 AC: 659 AN: 1461784 Hom.: 3 Cov.: 31 AF XY: 0.000384 AC XY: 279 AN XY: 727196

Gnomad4 AFR exome AF: 0.0116

Gnomad4 AMR exome AF: 0.000559

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000504

Gnomad4 SAS exome AF: 0.0000696

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000165

Gnomad4 OTH exome AF: 0.000894

GnomAD4 genome AF: 0.00351 AC: 535 AN: 152302 Hom.: 2 Cov.: 32 AF XY: 0.00336 AC XY: 250 AN XY: 74468

Gnomad4 AFR AF: 0.0121

Gnomad4 AMR AF: 0.00163

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000294

Gnomad4 OTH AF: 0.00189

Alfa AF: 0.000592 Hom.: 1

Bravo AF: 0.00403

TwinsUK AF: 0.000270 AC: 1

ALSPAC AF: 0.00 AC: 0

ESP6500AA AF: 0.0127 AC: 56

ESP6500EA AF: 0.000233 AC: 2

ExAC AF: 0.00124 AC: 151

Asia WGS AF: 0.000866 AC: 3 AN: 3478

EpiCase AF: 0.00

EpiControl AF: 0.000237

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jul 10, 2017

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.42	T
BayesDel_noAF	Benign	-0.37
Cadd	Pathogenic	33
Dann	Pathogenic	1.0
DEOGEN2	Benign	0.16	T;T
Eigen	Uncertain	0.61
Eigen_PC	Uncertain	0.61
FATHMM_MKL	Uncertain	0.92	D
M_CAP	Benign	0.012	T
MetaRNN	Benign	0.0049	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.2	M;M
MutationTaster	Benign	0.98	D;D;D;D
PrimateAI	Benign	0.41	T
Sift4G	Uncertain	0.027	D;D
Polyphen		1.0	D;D
Vest4		0.65
MutPred		0.24		Gain of solvent accessibility (P = 0.0037);Gain of solvent accessibility (P = 0.0037);
MVP		0.31
MPC		0.33
ClinPred		0.069	T
GERP RS		5.6
Varity_R		0.086
gMVP		0.52

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Pathogenic	1.0
dbscSNV1_RF	Pathogenic	1.0
SpliceAI score (max)		0.34		Details are displayed if max score is > 0.2
DS_DL_spliceai		0.34		Position offset: 0

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs61738671; hg19: chr18-43224125;