rs3214460

Variant names:

• chr19-32830811-A-G
• rs3214460
• NM_014270.5:c.1400-127T>C

Your query was ambiguous. Multiple possible variants found:

• chr19-32830811-A-G
• chr19-32830811-A-T

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.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
• Publications: 0 publications found

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]

SLC7A9 Gene-Disease associations (from GenCC):

• cystinuria

  Inheritance: AD, AR Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), ClinGen, Laboratory for Molecular Medicine
• cystinuria type B

  Inheritance: SD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -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 VariationId is 1226133.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.482 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014270.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC7A9	NM_014270.5	MANE Select	c.1400-127T>C		intron	N/A	NP_055085.1	P82251
	SLC7A9	NM_001126335.2		c.1400-127T>C		intron	N/A	NP_001119807.1	P82251
	SLC7A9	NM_001243036.2		c.1400-127T>C		intron	N/A	NP_001229965.1	P82251

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC7A9	ENST00000023064.9	TSL:1 MANE Select	c.1400-127T>C		intron	N/A	ENSP00000023064.3	P82251
	SLC7A9	ENST00000587772.1	TSL:1	c.1400-127T>C		intron	N/A	ENSP00000468439.1	P82251
	SLC7A9	ENST00000590341.5	TSL:1	c.1400-127T>C		intron	N/A	ENSP00000464822.1	P82251

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

African (AFR) AF: 0.265 AC: 4495 AN: 16958

American (AMR) AF: 0.540 AC: 18813 AN: 34818

Ashkenazi Jewish (ASJ) AF: 0.395 AC: 7766 AN: 19654

East Asian (EAS) AF: 0.141 AC: 4607 AN: 32714

South Asian (SAS) AF: 0.468 AC: 30220 AN: 64524

European-Finnish (FIN) AF: 0.472 AC: 20713 AN: 43856

Middle Eastern (MID) AF: 0.391 AC: 1590 AN: 4064

European-Non Finnish (NFE) AF: 0.487 AC: 171107 AN: 351604

Other (OTH) AF: 0.430 AC: 13547 AN: 31530

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

African (AFR) AF: 0.265 AC: 11017 AN: 41516

American (AMR) AF: 0.491 AC: 7493 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.397 AC: 1377 AN: 3468

East Asian (EAS) AF: 0.173 AC: 893 AN: 5168

South Asian (SAS) AF: 0.460 AC: 2215 AN: 4810

European-Finnish (FIN) AF: 0.464 AC: 4905 AN: 10572

Middle Eastern (MID) AF: 0.340 AC: 100 AN: 294

European-Non Finnish (NFE) AF: 0.481 AC: 32701 AN: 67952

Other (OTH) AF: 0.395 AC: 831 AN: 2106

Alfa AF: 0.375 Hom.: 2878

Bravo AF: 0.399

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.0020
DANN	Benign	0.35
PhyloP100		-4.3
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs3214460; hg19: chr19-33321717;