chr18-45727281-C-T

Variant names:

• chr18-45727281-C-T
• rs11877062
• NM_015865.7:c.-22+2268C>T

Variant summary

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

The NM_015865.7(SLC14A1):​c.-22+2268C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.476 in 1,550,698 control chromosomes in the GnomAD database, including 178,705 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.42 (14177 hom., cov: 33)
  • Exomes 𝑓: 0.48 (164528 hom.)
• Consequence: SLC14A1 NM_015865.7 intron
• Clinical Significance: Benign no assertion criteria provided B:1
• Conservation: PhyloP100: 0.597
• Publications: 30 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=3.8799644E-4).
• BP6: Variant 18-45727281-C-T is Benign according to our data. Variant chr18-45727281-C-T is described in ClinVar as Benign. ClinVar VariationId is 3060924.Status of the report is no_assertion_criteria_provided, 0 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.501 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_015865.7. 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.-22+2268C>T		intron	N/A	NP_056949.4
	SLC14A1	NM_001128588.4		c.10C>T	p.Arg4Trp	missense	Exon 3 of 11	NP_001122060.3
	SLC14A1	NM_001146037.1		c.10C>T	p.Arg4Trp	missense	Exon 1 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.-22+2268C>T		intron	N/A	ENSP00000318546.4
	SLC14A1	ENST00000535474.5	TSL:1	c.-56+2268C>T		intron	N/A	ENSP00000441998.1
	SLC14A1	ENST00000415427.7	TSL:2	c.10C>T	p.Arg4Trp	missense	Exon 3 of 11	ENSP00000412309.2

Frequencies

GnomAD3 genomes AF: 0.416 AC: 63251 AN: 151970 Hom.: 14179 Cov.: 33

Gnomad AFR AF: 0.234

Gnomad AMI AF: 0.363

Gnomad AMR AF: 0.477

Gnomad ASJ AF: 0.447

Gnomad EAS AF: 0.517

Gnomad SAS AF: 0.414

Gnomad FIN AF: 0.489

Gnomad MID AF: 0.434

Gnomad NFE AF: 0.493

Gnomad OTH AF: 0.443

GnomAD2 exomes AF: 0.474 AC: 73007 AN: 153972 AF XY: 0.472

Gnomad AFR exome AF: 0.234

Gnomad AMR exome AF: 0.512

Gnomad ASJ exome AF: 0.447

Gnomad EAS exome AF: 0.538

Gnomad FIN exome AF: 0.497

Gnomad NFE exome AF: 0.495

Gnomad OTH exome AF: 0.481

GnomAD4 exome AF: 0.482 AC: 674572 AN: 1398610 Hom.: 164528 Cov.: 42 AF XY: 0.481 AC XY: 331592 AN XY: 689858

African (AFR) AF: 0.228 AC: 7197 AN: 31588

American (AMR) AF: 0.512 AC: 18286 AN: 35700

Ashkenazi Jewish (ASJ) AF: 0.448 AC: 11287 AN: 25174

East Asian (EAS) AF: 0.542 AC: 19383 AN: 35738

South Asian (SAS) AF: 0.431 AC: 34109 AN: 79216

European-Finnish (FIN) AF: 0.499 AC: 24561 AN: 49242

Middle Eastern (MID) AF: 0.405 AC: 2293 AN: 5660

European-Non Finnish (NFE) AF: 0.492 AC: 530588 AN: 1078326

Other (OTH) AF: 0.464 AC: 26868 AN: 57966

GnomAD4 genome AF: 0.416 AC: 63259 AN: 152088 Hom.: 14177 Cov.: 33 AF XY: 0.415 AC XY: 30842 AN XY: 74346

African (AFR) AF: 0.234 AC: 9701 AN: 41506

American (AMR) AF: 0.476 AC: 7287 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.447 AC: 1550 AN: 3466

East Asian (EAS) AF: 0.518 AC: 2671 AN: 5160

South Asian (SAS) AF: 0.414 AC: 1997 AN: 4822

European-Finnish (FIN) AF: 0.489 AC: 5163 AN: 10568

Middle Eastern (MID) AF: 0.435 AC: 128 AN: 294

European-Non Finnish (NFE) AF: 0.493 AC: 33500 AN: 67956

Other (OTH) AF: 0.441 AC: 932 AN: 2114

Alfa AF: 0.449 Hom.: 21928

Bravo AF: 0.409

TwinsUK AF: 0.481 AC: 1784

ALSPAC AF: 0.489 AC: 1886

ESP6500AA AF: 0.212 AC: 293

ESP6500EA AF: 0.492 AC: 1567

ExAC AF: 0.416 AC: 9149

Asia WGS AF: 0.430 AC: 1500 AN: 3478

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	0.24
BayesDel_addAF	Benign	-0.71	T
BayesDel_noAF	Benign	-0.64
CADD	Benign	18
DANN	Uncertain	1.0
Eigen	Benign	-0.026
Eigen_PC	Benign	-0.070
FATHMM_MKL	Benign	0.22	N
LIST_S2	Benign	0.74	T
MetaRNN	Benign	0.00039	T
MetaSVM	Benign	-0.91	T
PhyloP100		0.60
PrimateAI	Benign	0.26	T
PROVEAN	Benign	-1.4	N
REVEL	Benign	0.084
Sift	Uncertain	0.0020	D
Sift4G	Uncertain	0.0020	D
Polyphen		0.99	D
Vest4		0.074
MPC		0.11
ClinPred		0.019	T
GERP RS		2.8
PromoterAI		-0.14	Neutral
gMVP		0.12
Mutation Taster		=300/0	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: rs11877062; hg19: chr18-43307246; COSMIC: COSV58933778; COSMIC: COSV58933778;