rs2287120

Positions:

• chr16-87837976-G-A
• chr16-87837976-G-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_003486.7(SLC7A5):​c.1044-35C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.225 in 1,494,576 control chromosomes in the GnomAD database, including 41,269 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.23 (4488 hom., cov: 34)
  • Exomes 𝑓: 0.22 (36781 hom.)
• Consequence: SLC7A5 NM_003486.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.10

Genes affected

SLC7A5 (HGNC:11063): (solute carrier family 7 member 5) Enables L-leucine transmembrane transporter activity; L-tryptophan transmembrane transporter activity; and thyroid hormone transmembrane transporter activity. Involved in carboxylic acid transport; thyroid hormone transport; and xenobiotic transport. Located in cytosol; intracellular membrane-bounded organelle; and plasma membrane. Is integral component of membrane. Part of amino acid transport complex; apical plasma membrane; and microvillus membrane. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.403 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLC7A5	NM_003486.7	c.1044-35C>T		intron_variant		ENST00000261622.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC7A5	ENST00000261622.5	c.1044-35C>T		intron_variant		1	NM_003486.7	P1
SLC7A5	ENST00000565644.5	c.246-35C>T		intron_variant		1

Frequencies

GnomAD3 genomes AF: 0.234 AC: 35627 AN: 152088 Hom.: 4472 Cov.: 34

Gnomad AFR AF: 0.263

Gnomad AMI AF: 0.442

Gnomad AMR AF: 0.241

Gnomad ASJ AF: 0.251

Gnomad EAS AF: 0.0599

Gnomad SAS AF: 0.419

Gnomad FIN AF: 0.158

Gnomad MID AF: 0.358

Gnomad NFE AF: 0.223

Gnomad OTH AF: 0.233

GnomAD3 exomes AF: 0.251 AC: 47038 AN: 187256 Hom.: 6666 AF XY: 0.263 AC XY: 26205 AN XY: 99708

Gnomad AFR exome AF: 0.273

Gnomad AMR exome AF: 0.256

Gnomad ASJ exome AF: 0.281

Gnomad EAS exome AF: 0.0670

Gnomad SAS exome AF: 0.428

Gnomad FIN exome AF: 0.168

Gnomad NFE exome AF: 0.237

Gnomad OTH exome AF: 0.255

GnomAD4 exome AF: 0.224 AC: 300568 AN: 1342370 Hom.: 36781 Cov.: 21 AF XY: 0.232 AC XY: 154895 AN XY: 668634

Gnomad4 AFR exome AF: 0.270

Gnomad4 AMR exome AF: 0.246

Gnomad4 ASJ exome AF: 0.275

Gnomad4 EAS exome AF: 0.0590

Gnomad4 SAS exome AF: 0.428

Gnomad4 FIN exome AF: 0.168

Gnomad4 NFE exome AF: 0.213

Gnomad4 OTH exome AF: 0.224

GnomAD4 genome AF: 0.234 AC: 35683 AN: 152206 Hom.: 4488 Cov.: 34 AF XY: 0.234 AC XY: 17453 AN XY: 74436

Gnomad4 AFR AF: 0.263

Gnomad4 AMR AF: 0.241

Gnomad4 ASJ AF: 0.251

Gnomad4 EAS AF: 0.0598

Gnomad4 SAS AF: 0.419

Gnomad4 FIN AF: 0.158

Gnomad4 NFE AF: 0.223

Gnomad4 OTH AF: 0.233

Alfa AF: 0.246 Hom.: 937

Bravo AF: 0.237

Asia WGS AF: 0.242 AC: 842 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.32
DANN	Benign	0.74
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		2.6

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: rs2287120; hg19: chr16-87871582; COSMIC: COSV55364555; COSMIC: COSV55364555;