chr19-32830811-A-G

Position:

• chr19-32830811-A-G

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_014270.5(SLC7A9):​c.1400-127T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.407 in 152,060 control chromosomes in the GnomAD database, including 13,512 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.41 (13512 hom., cov: 30)
  • Exomes 𝑓: 0.45 (65040 hom.)
  • Failed GnomAD Quality Control
• Consequence: SLC7A9 NM_014270.5 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -4.32

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

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.0).
• BP6: Variant 19-32830811-A-G is Benign according to our data. Variant chr19-32830811-A-G is described in ClinVar as [Benign]. Clinvar id is 1226133.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-32830811-A-G is described in Lovd as [Benign].
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.482 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLC7A9	NM_014270.5	c.1400-127T>C		intron_variant		ENST00000023064.9	NP_055085.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLC7A9	ENST00000023064.9	c.1400-127T>C		intron_variant		1	NM_014270.5	ENSP00000023064	P1

Frequencies

GnomAD3 genomes AF: 0.407 AC: 61867 AN: 151942 Hom.: 13503 Cov.: 30

Gnomad AFR AF: 0.266

Gnomad AMI AF: 0.396

Gnomad AMR AF: 0.490

Gnomad ASJ AF: 0.397

Gnomad EAS AF: 0.173

Gnomad SAS AF: 0.460

Gnomad FIN AF: 0.464

Gnomad MID AF: 0.345

Gnomad NFE AF: 0.481

Gnomad OTH AF: 0.394

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.455 AC: 272858 AN: 599722 Hom.: 65040 AF XY: 0.456 AC XY: 147124 AN XY: 322368

Gnomad4 AFR exome AF: 0.265

Gnomad4 AMR exome AF: 0.540

Gnomad4 ASJ exome AF: 0.395

Gnomad4 EAS exome AF: 0.141

Gnomad4 SAS exome AF: 0.468

Gnomad4 FIN exome AF: 0.472

Gnomad4 NFE exome AF: 0.487

Gnomad4 OTH exome AF: 0.430

GnomAD4 genome AF: 0.407 AC: 61892 AN: 152060 Hom.: 13512 Cov.: 30 AF XY: 0.408 AC XY: 30301 AN XY: 74320

Gnomad4 AFR AF: 0.265

Gnomad4 AMR AF: 0.491

Gnomad4 ASJ AF: 0.397

Gnomad4 EAS AF: 0.173

Gnomad4 SAS AF: 0.460

Gnomad4 FIN AF: 0.464

Gnomad4 NFE AF: 0.481

Gnomad4 OTH AF: 0.395

Alfa AF: 0.434 Hom.: 2253

Bravo AF: 0.399

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Dec 08, 2019	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.0020
DANN	Benign	0.35

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		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: rs3214460; hg19: chr19-33321717;