rs2298720

Variant names:

• chr18-45730450-G-A
• rs2298720
• NM_015865.7:c.130G>A

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP6 BA1

The ENST00000321925.9(SLC14A1):​c.130G>A​(p.Glu44Lys) variant causes a missense change. The variant allele was found at a frequency of 0.102 in 1,613,960 control chromosomes in the GnomAD database, including 13,402 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.14 (1962 hom., cov: 32)
  • Exomes 𝑓: 0.099 (11440 hom.)
• Consequence: SLC14A1 ENST00000321925.9 missense
• Clinical Significance: Benign no assertion criteria provided B:1
• Conservation: PhyloP100: 4.35
• Publications: 50 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 -13 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.00406754).
• BP6: Variant 18-45730450-G-A is Benign according to our data. Variant chr18-45730450-G-A is described in ClinVar as Benign. ClinVar VariationId is 3059300.Status of the report is no_assertion_criteria_provided, 0 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.391 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000321925.9. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC14A1	NM_015865.7	MANE Select	c.130G>A	p.Glu44Lys	missense	Exon 3 of 10	NP_056949.4
	SLC14A1	NM_001128588.4		c.298G>A	p.Glu100Lys	missense	Exon 4 of 11	NP_001122060.3
	SLC14A1	NM_001146037.1		c.298G>A	p.Glu100Lys	missense	Exon 2 of 9	NP_001139509.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC14A1	ENST00000321925.9	TSL:1 MANE Select	c.130G>A	p.Glu44Lys	missense	Exon 3 of 10	ENSP00000318546.4
	SLC14A1	ENST00000586142.5	TSL:1	c.130G>A	p.Glu44Lys	missense	Exon 1 of 8	ENSP00000470476.1
	SLC14A1	ENST00000589700.5	TSL:1	c.130G>A	p.Glu44Lys	missense	Exon 1 of 7	ENSP00000465044.1

Frequencies

GnomAD3 genomes AF: 0.138 AC: 20915 AN: 152026 Hom.: 1959 Cov.: 32

Gnomad AFR AF: 0.197

Gnomad AMI AF: 0.0318

Gnomad AMR AF: 0.183

Gnomad ASJ AF: 0.101

Gnomad EAS AF: 0.406

Gnomad SAS AF: 0.268

Gnomad FIN AF: 0.123

Gnomad MID AF: 0.0759

Gnomad NFE AF: 0.0679

Gnomad OTH AF: 0.113

GnomAD2 exomes AF: 0.152 AC: 38188 AN: 251310 AF XY: 0.148

Gnomad AFR exome AF: 0.200

Gnomad AMR exome AF: 0.235

Gnomad ASJ exome AF: 0.102

Gnomad EAS exome AF: 0.392

Gnomad FIN exome AF: 0.119

Gnomad NFE exome AF: 0.0652

Gnomad OTH exome AF: 0.120

GnomAD4 exome AF: 0.0988 AC: 144449 AN: 1461816 Hom.: 11440 Cov.: 32 AF XY: 0.102 AC XY: 74446 AN XY: 727212

African (AFR) AF: 0.199 AC: 6677 AN: 33476

American (AMR) AF: 0.225 AC: 10059 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.0998 AC: 2607 AN: 26134

East Asian (EAS) AF: 0.390 AC: 15473 AN: 39694

South Asian (SAS) AF: 0.254 AC: 21884 AN: 86248

European-Finnish (FIN) AF: 0.116 AC: 6198 AN: 53420

Middle Eastern (MID) AF: 0.0957 AC: 552 AN: 5768

European-Non Finnish (NFE) AF: 0.0665 AC: 73895 AN: 1111956

Other (OTH) AF: 0.118 AC: 7104 AN: 60396

GnomAD4 genome AF: 0.138 AC: 20943 AN: 152144 Hom.: 1962 Cov.: 32 AF XY: 0.145 AC XY: 10772 AN XY: 74382

African (AFR) AF: 0.197 AC: 8183 AN: 41484

American (AMR) AF: 0.184 AC: 2815 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.101 AC: 349 AN: 3470

East Asian (EAS) AF: 0.405 AC: 2090 AN: 5160

South Asian (SAS) AF: 0.268 AC: 1291 AN: 4816

European-Finnish (FIN) AF: 0.123 AC: 1303 AN: 10594

Middle Eastern (MID) AF: 0.0816 AC: 24 AN: 294

European-Non Finnish (NFE) AF: 0.0680 AC: 4621 AN: 68004

Other (OTH) AF: 0.113 AC: 238 AN: 2114

Alfa AF: 0.100 Hom.: 2891

Bravo AF: 0.143

TwinsUK AF: 0.0653 AC: 242

ALSPAC AF: 0.0703 AC: 271

ESP6500AA AF: 0.193 AC: 849

ESP6500EA AF: 0.0649 AC: 558

ExAC AF: 0.147 AC: 17904

Asia WGS AF: 0.316 AC: 1095 AN: 3478

EpiCase AF: 0.0663

EpiControl AF: 0.0680

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
-	-	1	SLC14A1-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.48	T
BayesDel_noAF	Benign	-0.32
CADD	Benign	22
DANN	Uncertain	1.0
DEOGEN2	Benign	0.40	T
Eigen	Uncertain	0.29
Eigen_PC	Uncertain	0.29
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Benign	0.73	T
MetaRNN	Benign	0.0041	T
MetaSVM	Benign	-0.97	T
MutationAssessor	Pathogenic	3.2	M
PhyloP100		4.4
PrimateAI	Benign	0.47	T
PROVEAN	Uncertain	-2.7	D
REVEL	Benign	0.16
Sift	Uncertain	0.012	D
Sift4G	Uncertain	0.026	D
Polyphen		0.45	B
Vest4		0.43
MPC		0.33
ClinPred		0.050	T
GERP RS		5.0
PromoterAI		-0.045	Neutral
Varity_R		0.46
gMVP		0.36
Mutation Taster		=95/5	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.17		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: rs2298720; hg19: chr18-43310415; COSMIC: COSV58931147; COSMIC: COSV58931147;