rs2287884

Variant names:

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

Your query was ambiguous. Multiple possible variants found:

• chr19-32830541-A-G
• chr19-32830541-A-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
• Publications: 12 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: AR, AD Classification: DEFINITIVE, STRONG Submitted by: PanelApp Australia, Labcorp Genetics (formerly Invitae), Laboratory for Molecular Medicine, ClinGen
• 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=-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 VariationId is 328740.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.193 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.*79T>C		3_prime_UTR	Exon 13 of 13	NP_055085.1	P82251
	SLC7A9	NM_001126335.2		c.*79T>C		3_prime_UTR	Exon 13 of 13	NP_001119807.1	P82251
	SLC7A9	NM_001243036.2		c.*79T>C		3_prime_UTR	Exon 13 of 13	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.*79T>C		3_prime_UTR	Exon 13 of 13	ENSP00000023064.3	P82251
	SLC7A9	ENST00000590341.5	TSL:1	c.*79T>C		3_prime_UTR	Exon 13 of 13	ENSP00000464822.1	P82251
	SLC7A9	ENST00000879205.1		c.*79T>C		3_prime_UTR	Exon 13 of 13	ENSP00000549264.1

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

African (AFR) AF: 0.196 AC: 4538 AN: 23152

American (AMR) AF: 0.100 AC: 4383 AN: 43754

Ashkenazi Jewish (ASJ) AF: 0.139 AC: 3164 AN: 22826

East Asian (EAS) AF: 0.209 AC: 7762 AN: 37194

South Asian (SAS) AF: 0.130 AC: 9807 AN: 75358

European-Finnish (FIN) AF: 0.216 AC: 11447 AN: 52886

Middle Eastern (MID) AF: 0.138 AC: 486 AN: 3518

European-Non Finnish (NFE) AF: 0.163 AC: 103262 AN: 632836

Other (OTH) 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

African (AFR) AF: 0.197 AC: 8170 AN: 41514

American (AMR) AF: 0.127 AC: 1946 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.142 AC: 494 AN: 3472

East Asian (EAS) AF: 0.200 AC: 1036 AN: 5172

South Asian (SAS) AF: 0.123 AC: 596 AN: 4830

European-Finnish (FIN) AF: 0.235 AC: 2492 AN: 10592

Middle Eastern (MID) AF: 0.158 AC: 46 AN: 292

European-Non Finnish (NFE) AF: 0.166 AC: 11260 AN: 67998

Other (OTH) AF: 0.169 AC: 358 AN: 2114

Alfa AF: 0.155 Hom.: 2362

Bravo AF: 0.169

Asia WGS AF: 0.188 AC: 653 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	1	Cystinuria (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	12
DANN	Benign	0.64
PhyloP100		0.41
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

Other links and lift over

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