rs3815559

Positions:

• chr16-87837760-G-C

Variant summary

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

The ENST00000261622.5(SLC7A5):​c.1140+85C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.229 in 1,113,994 control chromosomes in the GnomAD database, including 32,574 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 0.24 (4616 hom., cov: 35)
  • Exomes 𝑓: 0.23 (27958 hom.)
• Consequence: SLC7A5 ENST00000261622.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.69

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=-0.85).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.404 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLC7A5	NM_003486.7	c.1140+85C>G		intron_variant		ENST00000261622.5	NP_003477.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLC7A5	ENST00000261622.5	c.1140+85C>G		intron_variant		1	NM_003486.7	ENSP00000261622	P1
SLC7A5	ENST00000565644.5	c.342+85C>G		intron_variant		1		ENSP00000454323

Frequencies

GnomAD3 genomes AF: 0.237 AC: 36093 AN: 152140 Hom.: 4600 Cov.: 35

Gnomad AFR AF: 0.273

Gnomad AMI AF: 0.441

Gnomad AMR AF: 0.242

Gnomad ASJ AF: 0.247

Gnomad EAS AF: 0.0596

Gnomad SAS AF: 0.420

Gnomad FIN AF: 0.159

Gnomad MID AF: 0.358

Gnomad NFE AF: 0.223

Gnomad OTH AF: 0.236

GnomAD4 exome AF: 0.228 AC: 219111 AN: 961736 Hom.: 27958 Cov.: 13 AF XY: 0.237 AC XY: 115982 AN XY: 489422

Gnomad4 AFR exome AF: 0.277

Gnomad4 AMR exome AF: 0.246

Gnomad4 ASJ exome AF: 0.270

Gnomad4 EAS exome AF: 0.0589

Gnomad4 SAS exome AF: 0.429

Gnomad4 FIN exome AF: 0.168

Gnomad4 NFE exome AF: 0.215

Gnomad4 OTH exome AF: 0.227

GnomAD4 genome AF: 0.237 AC: 36147 AN: 152258 Hom.: 4616 Cov.: 35 AF XY: 0.237 AC XY: 17667 AN XY: 74434

Gnomad4 AFR AF: 0.274

Gnomad4 AMR AF: 0.242

Gnomad4 ASJ AF: 0.247

Gnomad4 EAS AF: 0.0595

Gnomad4 SAS AF: 0.420

Gnomad4 FIN AF: 0.159

Gnomad4 NFE AF: 0.223

Gnomad4 OTH AF: 0.235

Alfa AF: 0.246 Hom.: 572

Bravo AF: 0.240

Asia WGS AF: 0.241 AC: 839 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	0.12
DANN	Benign	0.53
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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: rs3815559; hg19: chr16-87871366; COSMIC: COSV55363603; COSMIC: COSV55363603;