18-45731166-G-A

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_Strong BP6_Moderate BP7 BA1

The NM_015865.7(SLC14A1):c.303G>A(p.Val101=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00495 in 1,614,000 control chromosomes in the GnomAD database, including 234 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.022 (113 hom., cov: 32)
  • Exomes 𝑓: 0.0032 (121 hom.)
• Consequence: SLC14A1 NM_015865.7 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.93

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 -15 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.63).
• BP6: Variant 18-45731166-G-A is Benign according to our data. Variant chr18-45731166-G-A is described in ClinVar as [Benign]. Clinvar id is 773343.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=1.93 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0692 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLC14A1	NM_015865.7	c.303G>A	p.Val101=	synonymous_variant	4/10	ENST00000321925.9
LOC105372093	XR_935423.3	n.826+6300C>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC14A1	ENST00000321925.9	c.303G>A	p.Val101=	synonymous_variant	4/10	1	NM_015865.7	P1
	ENST00000589510.5	n.160+6300C>T		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.0218 AC: 3318 AN: 152172 Hom.: 112 Cov.: 32

Gnomad AFR AF: 0.0713

Gnomad AMI AF: 0.00110

Gnomad AMR AF: 0.0148

Gnomad ASJ AF: 0.000864

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00104

Gnomad FIN AF: 0.0000941

Gnomad MID AF: 0.0316

Gnomad NFE AF: 0.00129

Gnomad OTH AF: 0.0144

GnomAD3 exomes AF: 0.00664 AC: 1670 AN: 251366 Hom.: 47 AF XY: 0.00518 AC XY: 703 AN XY: 135840

Gnomad AFR exome AF: 0.0719

Gnomad AMR exome AF: 0.00633

Gnomad ASJ exome AF: 0.00169

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000588

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00187

Gnomad OTH exome AF: 0.00571

GnomAD4 exome AF: 0.00320 AC: 4671 AN: 1461710 Hom.: 121 Cov.: 32 AF XY: 0.00294 AC XY: 2138 AN XY: 727154

Gnomad4 AFR exome AF: 0.0736

Gnomad4 AMR exome AF: 0.00727

Gnomad4 ASJ exome AF: 0.00157

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000649

Gnomad4 FIN exome AF: 0.0000187

Gnomad4 NFE exome AF: 0.00105

Gnomad4 OTH exome AF: 0.00856

GnomAD4 genome AF: 0.0218 AC: 3324 AN: 152290 Hom.: 113 Cov.: 32 AF XY: 0.0216 AC XY: 1606 AN XY: 74472

Gnomad4 AFR AF: 0.0713

Gnomad4 AMR AF: 0.0147

Gnomad4 ASJ AF: 0.000864

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000830

Gnomad4 FIN AF: 0.0000941

Gnomad4 NFE AF: 0.00128

Gnomad4 OTH AF: 0.0142

Alfa AF: 0.00604 Hom.: 39

Bravo AF: 0.0256

Asia WGS AF: 0.00924 AC: 32 AN: 3478

EpiCase AF: 0.00289

EpiControl AF: 0.00279

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jul 23, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.63
Cadd	Benign	9.1
Dann	Benign	0.72

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs28994287; hg19: chr18-43311131;