19-32830541-A-G

Variant names:

• chr19-32830541-A-G
• rs2287884
• NM_014270.5:c.*79T>C

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_014270.5(SLC7A9):​c.*79T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.164 in 1,086,512 control chromosomes in the GnomAD database, including 15,484 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.17 (2442 hom., cov: 32)
  • Exomes 𝑓: 0.16 (13042 hom.)
• Consequence: SLC7A9 NM_014270.5 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 0.408

Genes affected

SLC7A9 (HGNC:11067): (solute carrier family 7 member 9) This gene encodes a protein that belongs to a family of light subunits of amino acid transporters. This protein plays a role in the high-affinity and sodium-independent transport of cystine and neutral and dibasic amino acids, and appears to function in the reabsorption of cystine in the kidney tubule. Mutations in this gene cause non-type I cystinuria, a disease that leads to cystine stones in the urinary system due to impaired transport of cystine and dibasic amino acids. Alternate transcript variants, which encode the same protein, have been found for this gene. [provided by RefSeq, Jul 2011]

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BP6: Variant 19-32830541-A-G is Benign according to our data. Variant chr19-32830541-A-G is described in ClinVar as [Benign]. Clinvar id is 328740.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-32830541-A-G is described in Lovd as [Benign].
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.193 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC7A9	NM_014270.5	c.*79T>C		3_prime_UTR_variant	Exon 13 of 13	ENST00000023064.9	NP_055085.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC7A9	ENST00000023064	c.*79T>C		3_prime_UTR_variant	Exon 13 of 13	1	NM_014270.5	ENSP00000023064.3

Frequencies

GnomAD3 genomes AF: 0.174 AC: 26531 AN: 152058 Hom.: 2438 Cov.: 32

Gnomad AFR AF: 0.197

Gnomad AMI AF: 0.178

Gnomad AMR AF: 0.128

Gnomad ASJ AF: 0.142

Gnomad EAS AF: 0.200

Gnomad SAS AF: 0.124

Gnomad FIN AF: 0.235

Gnomad MID AF: 0.156

Gnomad NFE AF: 0.166

Gnomad OTH AF: 0.165

GnomAD4 exome AF: 0.163 AC: 152149 AN: 934336 Hom.: 13042 Cov.: 13 AF XY: 0.162 AC XY: 78821 AN XY: 488020

Gnomad4 AFR exome AF: 0.196 AC: 4538 AN: 23152

Gnomad4 AMR exome AF: 0.100 AC: 4383 AN: 43754

Gnomad4 ASJ exome AF: 0.139 AC: 3164 AN: 22826

Gnomad4 EAS exome AF: 0.209 AC: 7762 AN: 37194

Gnomad4 SAS exome AF: 0.130 AC: 9807 AN: 75358

Gnomad4 FIN exome AF: 0.216 AC: 11447 AN: 52886

Gnomad4 NFE exome AF: 0.163 AC: 103262 AN: 632836

Gnomad4 Remaining exome AF: 0.171 AC: 7300 AN: 42812

GnomAD4 genome AF: 0.175 AC: 26559 AN: 152176 Hom.: 2442 Cov.: 32 AF XY: 0.174 AC XY: 12979 AN XY: 74402

Gnomad4 AFR AF: 0.197 AC: 0.196801 AN: 0.196801

Gnomad4 AMR AF: 0.127 AC: 0.127306 AN: 0.127306

Gnomad4 ASJ AF: 0.142 AC: 0.142281 AN: 0.142281

Gnomad4 EAS AF: 0.200 AC: 0.200309 AN: 0.200309

Gnomad4 SAS AF: 0.123 AC: 0.123395 AN: 0.123395

Gnomad4 FIN AF: 0.235 AC: 0.235272 AN: 0.235272

Gnomad4 NFE AF: 0.166 AC: 0.165593 AN: 0.165593

Gnomad4 OTH AF: 0.169 AC: 0.169347 AN: 0.169347

Alfa AF: 0.155 Hom.: 2362

Bravo AF: 0.169

Asia WGS AF: 0.188 AC: 653 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Jan 11, 2020

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Cystinuria Benign:1

Jan 13, 2018

Illumina Laboratory Services, Illumina

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	12
DANN	Benign	0.64
Mutation Taster		=100/0	polymorphism

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

Publications

LitVar

Other links and lift over

dbSNP: rs2287884; hg19: chr19-33321447; COSMIC: COSV50086312; COSMIC: COSV50086312;