rs1058396

chr18-45739554-G-Achr18-45739554-G-Cchr18-45739554-G-T

Variant summary

Our verdict is Benign. Variant got -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. 14/19 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:2
• Conservation: PhyloP100: 0.723

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]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -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 id 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/exons	MANE	UniProt
SLC14A1	NM_015865.7	c.838G>A	p.Asp280Asn	missense_variant	8/10	ENST00000321925.9
LOC105372093	XR_935423.3	n.698-1960C>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC14A1	ENST00000321925.9	c.838G>A	p.Asp280Asn	missense_variant	8/10	1	NM_015865.7	P1
	ENST00000589510.5	n.31+1543C>T		intron_variant, non_coding_transcript_variant		5

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

GnomAD3 exomes AF: 0.471 AC: 118542 AN: 251432 Hom.: 28469 AF XY: 0.472 AC XY: 64136 AN XY: 135894

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 SAS exome AF: 0.424

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

Gnomad4 AFR exome AF: 0.265

Gnomad4 AMR exome AF: 0.515

Gnomad4 ASJ exome AF: 0.433

Gnomad4 EAS exome AF: 0.540

Gnomad4 SAS exome AF: 0.428

Gnomad4 FIN exome AF: 0.490

Gnomad4 NFE exome AF: 0.481

Gnomad4 OTH exome AF: 0.457

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

Gnomad4 AFR AF: 0.269

Gnomad4 AMR AF: 0.477

Gnomad4 ASJ AF: 0.427

Gnomad4 EAS AF: 0.518

Gnomad4 SAS AF: 0.406

Gnomad4 FIN AF: 0.479

Gnomad4 NFE AF: 0.484

Gnomad4 OTH AF: 0.444

Alfa AF: 0.474 Hom.: 45195

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:2

Revision: criteria provided, single submitter

Submissions by phenotype

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

Benign, no assertion criteria provided

literature only

OMIM

Jul 01, 1997

- -

SLC14A1-related condition Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Oct 17, 2019

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). -

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
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
MutationTaster	Benign	1.0	P;P;P;P;P;P;P;P;P;P
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
Polyphen		0.0010	B;B;B;.;B;.;.;B;B
Vest4		0.026
MPC		0.10
ClinPred		0.0025	T
GERP RS		-7.6
Varity_R		0.079
gMVP		0.61

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

Publications

LitVar

Other links and lift over

dbSNP: rs1058396; hg19: chr18-43319519; COSMIC: COSV58931361; COSMIC: COSV58931361;