rs1058396

Variant names:

• chr18-45739554-G-A
• rs1058396
• NM_015865.7:c.838G>A

Your query was ambiguous. Multiple possible variants found:

• chr18-45739554-G-A
• chr18-45739554-G-C
• chr18-45739554-G-T

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_015865.7(SLC14A1):​c.838G>A​(p.Asp280Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.469 in 1,613,474 control chromosomes in the GnomAD database, including 180,070 homozygotes. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.42 (14195 hom., cov: 31)
  • Exomes 𝑓: 0.47 (165875 hom.)
• Consequence: SLC14A1 NM_015865.7 missense
• Clinical Significance: Benign criteria provided, single submitter B:3
• Conservation: PhyloP100: 0.723
• Publications: 83 publications found

Genes affected

SLC14A1 (HGNC:10918): (solute carrier family 14 member 1 (Kidd blood group)) The protein encoded by this gene is a membrane transporter that mediates urea transport in erythrocytes. This gene forms the basis for the Kidd blood group system. [provided by RefSeq, Mar 2009]

ENSG00000288545 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=2.9844046E-4).
• BP6: Variant 18-45739554-G-A is Benign according to our data. Variant chr18-45739554-G-A is described in ClinVar as Benign. ClinVar VariationId is 17717.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.502 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC14A1	NM_015865.7	c.838G>A	p.Asp280Asn	missense_variant	Exon 8 of 10	ENST00000321925.9	NP_056949.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC14A1	ENST00000321925.9	c.838G>A	p.Asp280Asn	missense_variant	Exon 8 of 10	1	NM_015865.7	ENSP00000318546.4

Frequencies

GnomAD3 genomes AF: 0.421 AC: 63870 AN: 151798 Hom.: 14196 Cov.: 31

Gnomad AFR AF: 0.269

Gnomad AMI AF: 0.365

Gnomad AMR AF: 0.477

Gnomad ASJ AF: 0.427

Gnomad EAS AF: 0.518

Gnomad SAS AF: 0.407

Gnomad FIN AF: 0.479

Gnomad MID AF: 0.430

Gnomad NFE AF: 0.484

Gnomad OTH AF: 0.446

GnomAD2 exomes AF: 0.471 AC: 118542 AN: 251432 AF XY: 0.472

Gnomad AFR exome AF: 0.267

Gnomad AMR exome AF: 0.515

Gnomad ASJ exome AF: 0.434

Gnomad EAS exome AF: 0.536

Gnomad FIN exome AF: 0.490

Gnomad NFE exome AF: 0.489

Gnomad OTH exome AF: 0.476

GnomAD4 exome AF: 0.474 AC: 693015 AN: 1461558 Hom.: 165875 Cov.: 43 AF XY: 0.473 AC XY: 343901 AN XY: 727102

African (AFR) AF: 0.265 AC: 8882 AN: 33472

American (AMR) AF: 0.515 AC: 23046 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.433 AC: 11316 AN: 26136

East Asian (EAS) AF: 0.540 AC: 21451 AN: 39700

South Asian (SAS) AF: 0.428 AC: 36948 AN: 86254

European-Finnish (FIN) AF: 0.490 AC: 26183 AN: 53416

Middle Eastern (MID) AF: 0.409 AC: 2360 AN: 5768

European-Non Finnish (NFE) AF: 0.481 AC: 535245 AN: 1111706

Other (OTH) AF: 0.457 AC: 27584 AN: 60384

GnomAD4 genome AF: 0.421 AC: 63882 AN: 151916 Hom.: 14195 Cov.: 31 AF XY: 0.419 AC XY: 31078 AN XY: 74244

African (AFR) AF: 0.269 AC: 11151 AN: 41426

American (AMR) AF: 0.477 AC: 7288 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.427 AC: 1479 AN: 3466

East Asian (EAS) AF: 0.518 AC: 2666 AN: 5144

South Asian (SAS) AF: 0.406 AC: 1953 AN: 4810

European-Finnish (FIN) AF: 0.479 AC: 5062 AN: 10562

Middle Eastern (MID) AF: 0.432 AC: 127 AN: 294

European-Non Finnish (NFE) AF: 0.484 AC: 32890 AN: 67918

Other (OTH) AF: 0.444 AC: 934 AN: 2102

Alfa AF: 0.464 Hom.: 65920

Bravo AF: 0.415

TwinsUK AF: 0.472 AC: 1751

ALSPAC AF: 0.477 AC: 1839

ESP6500AA AF: 0.265 AC: 1169

ESP6500EA AF: 0.486 AC: 4177

ExAC AF: 0.469 AC: 56994

Asia WGS AF: 0.428 AC: 1494 AN: 3478

EpiCase AF: 0.478

EpiControl AF: 0.480

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

SLC14A1-related disorder Benign:1

Oct 17, 2019

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications).

KIDD BLOOD POLYMORPHISM Jk(a)/Jk(b) Benign:1

Jul 01, 1997

OMIM

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: literature only

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.069
BayesDel_addAF	Benign	-0.69	T
BayesDel_noAF	Benign	-0.62
CADD	Benign	3.9
DANN	Benign	0.74
DEOGEN2	Benign	0.025	T;T;.;.;T;.;.;.;T
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.095	N
LIST_S2	Benign	0.0	.;T;.;.;.;T;T;T;T
MetaRNN	Benign	0.00030	T;T;T;T;T;T;T;T;T
MetaSVM	Benign	-0.95	T
MutationAssessor	Benign	0.72	N;.;.;.;N;.;.;.;N
PhyloP100		0.72
PrimateAI	Benign	0.30	T
PROVEAN	Benign	-0.22	N;N;N;.;.;N;N;N;.
REVEL	Benign	0.061
Sift	Benign	0.59	T;T;T;.;.;T;T;T;.
Sift4G	Benign	0.64	T;T;T;T;.;T;T;T;T
Vest4		0.026
ClinPred		0.0025	T
GERP RS		-7.6
Varity_R		0.079
gMVP		0.61
Mutation Taster		=296/4	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		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: rs1058396; hg19: chr18-43319519; COSMIC: COSV58931361; COSMIC: COSV58931361;