18-45596371-T-C

Variant names:

• chr18-45596371-T-C
• rs959246
• NM_001242692.2:c.-34-28260T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001242692.2(SLC14A2):​c.-34-28260T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.736 in 152,164 control chromosomes in the GnomAD database, including 41,461 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.74 (41461 hom., cov: 32)
• Consequence: SLC14A2 NM_001242692.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.57
• Publications: 7 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 (BayesDel_noAF=-0.99).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.831 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC14A2	NM_001242692.2	c.-34-28260T>C		intron_variant	Intron 2 of 20		NP_001229621.1
SLC14A2	NM_001371319.1	c.-34-28260T>C		intron_variant	Intron 5 of 23		NP_001358248.1
SLC14A2	XM_024451270.2	c.-34-28260T>C		intron_variant	Intron 3 of 21		XP_024307038.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC14A2	ENST00000586448.5	c.-34-28260T>C		intron_variant	Intron 2 of 20	2		ENSP00000465953.1
ENSG00000287943	ENST00000658918.1	n.76+15094A>G		intron_variant	Intron 1 of 1
ENSG00000287943	ENST00000729208.1	n.278+15120A>G		intron_variant	Intron 2 of 2
ENSG00000287943	ENST00000729209.1	n.440+15120A>G		intron_variant	Intron 3 of 3

Frequencies

GnomAD3 genomes AF: 0.736 AC: 111937 AN: 152046 Hom.: 41425 Cov.: 32

Gnomad AFR AF: 0.764

Gnomad AMI AF: 0.753

Gnomad AMR AF: 0.758

Gnomad ASJ AF: 0.647

Gnomad EAS AF: 0.852

Gnomad SAS AF: 0.801

Gnomad FIN AF: 0.660

Gnomad MID AF: 0.680

Gnomad NFE AF: 0.718

Gnomad OTH AF: 0.719

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.736 AC: 112022 AN: 152164 Hom.: 41461 Cov.: 32 AF XY: 0.735 AC XY: 54681 AN XY: 74394

African (AFR) AF: 0.764 AC: 31720 AN: 41514

American (AMR) AF: 0.757 AC: 11582 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.647 AC: 2247 AN: 3472

East Asian (EAS) AF: 0.852 AC: 4411 AN: 5180

South Asian (SAS) AF: 0.802 AC: 3868 AN: 4824

European-Finnish (FIN) AF: 0.660 AC: 6977 AN: 10578

Middle Eastern (MID) AF: 0.680 AC: 200 AN: 294

European-Non Finnish (NFE) AF: 0.718 AC: 48808 AN: 67994

Other (OTH) AF: 0.723 AC: 1525 AN: 2110

Alfa AF: 0.717 Hom.: 9473

Bravo AF: 0.743

Asia WGS AF: 0.803 AC: 2794 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	0.44
DANN	Benign	0.43
PhyloP100		-1.6
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs959246; hg19: chr18-43176336;