18-45729946-C-T

Variant names:

• chr18-45729946-C-T
• rs17674580
• ENST00000586142.5:c.-375C>T

Variant summary

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

The ENST00000586142.5(SLC14A1):​c.-375C>T variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.26 in 175,308 control chromosomes in the GnomAD database, including 7,367 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 0.25 (6220 hom., cov: 33)
  • Exomes 𝑓: 0.29 (1147 hom.)
• Consequence: SLC14A1 ENST00000586142.5 5_prime_UTR_premature_start_codon_gain
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.539
• Publications: 37 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.357 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC14A1	NM_015865.7	c.-21-354C>T		intron_variant	Intron 2 of 9	ENST00000321925.9	NP_056949.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC14A1	ENST00000321925.9	c.-21-354C>T		intron_variant	Intron 2 of 9	1	NM_015865.7	ENSP00000318546.4

Frequencies

GnomAD3 genomes AF: 0.255 AC: 38701 AN: 151996 Hom.: 6218 Cov.: 33

Gnomad AFR AF: 0.0755

Gnomad AMI AF: 0.580

Gnomad AMR AF: 0.230

Gnomad ASJ AF: 0.345

Gnomad EAS AF: 0.0748

Gnomad SAS AF: 0.292

Gnomad FIN AF: 0.312

Gnomad MID AF: 0.379

Gnomad NFE AF: 0.361

Gnomad OTH AF: 0.279

GnomAD4 exome AF: 0.294 AC: 6830 AN: 23194 Hom.: 1147 Cov.: 0 AF XY: 0.296 AC XY: 3498 AN XY: 11822

African (AFR) AF: 0.0673 AC: 54 AN: 802

American (AMR) AF: 0.217 AC: 489 AN: 2256

Ashkenazi Jewish (ASJ) AF: 0.329 AC: 262 AN: 796

East Asian (EAS) AF: 0.0615 AC: 112 AN: 1822

South Asian (SAS) AF: 0.303 AC: 298 AN: 984

European-Finnish (FIN) AF: 0.300 AC: 202 AN: 674

Middle Eastern (MID) AF: 0.352 AC: 31 AN: 88

European-Non Finnish (NFE) AF: 0.346 AC: 5001 AN: 14434

Other (OTH) AF: 0.285 AC: 381 AN: 1338

GnomAD4 genome AF: 0.254 AC: 38703 AN: 152114 Hom.: 6220 Cov.: 33 AF XY: 0.253 AC XY: 18839 AN XY: 74354

African (AFR) AF: 0.0754 AC: 3129 AN: 41520

American (AMR) AF: 0.230 AC: 3507 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.345 AC: 1198 AN: 3468

East Asian (EAS) AF: 0.0750 AC: 389 AN: 5188

South Asian (SAS) AF: 0.292 AC: 1407 AN: 4820

European-Finnish (FIN) AF: 0.312 AC: 3294 AN: 10560

Middle Eastern (MID) AF: 0.366 AC: 107 AN: 292

European-Non Finnish (NFE) AF: 0.361 AC: 24548 AN: 67970

Other (OTH) AF: 0.282 AC: 596 AN: 2110

Alfa AF: 0.322 Hom.: 28650

Bravo AF: 0.237

Asia WGS AF: 0.201 AC: 696 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.38
DANN	Benign	0.63
PhyloP100		-0.54
PromoterAI		-0.013	Neutral
Mutation Taster		=300/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs17674580; hg19: chr18-43309911;