rs2287120

Variant names:

• chr16-87837976-G-A
• rs2287120
• NM_003486.7:c.1044-35C>T

Your query was ambiguous. Multiple possible variants found:

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

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 9 publications found

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]

SLC7A5 Gene-Disease associations (from GenCC):

• complex neurodevelopmental disorder

  Inheritance: AR Classification: MODERATE, LIMITED Submitted by: ClinGen, Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003486.7. 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
	SLC7A5	NM_003486.7	MANE Select	c.1044-35C>T		intron	N/A	NP_003477.4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC7A5	ENST00000261622.5	TSL:1 MANE Select	c.1044-35C>T		intron	N/A	ENSP00000261622.4	Q01650
	SLC7A5	ENST00000565644.6	TSL:1	c.246-35C>T		intron	N/A	ENSP00000454323.1	A0A0C4DGL4
	SLC7A5	ENST00000850914.1		c.1098-35C>T		intron	N/A	ENSP00000520997.1	A0ABJ7H8K0

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

GnomAD2 exomes AF: 0.251 AC: 47038 AN: 187256 AF XY: 0.263

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 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

African (AFR) AF: 0.270 AC: 8511 AN: 31580

American (AMR) AF: 0.246 AC: 9238 AN: 37502

Ashkenazi Jewish (ASJ) AF: 0.275 AC: 6839 AN: 24882

East Asian (EAS) AF: 0.0590 AC: 2250 AN: 38164

South Asian (SAS) AF: 0.428 AC: 34043 AN: 79472

European-Finnish (FIN) AF: 0.168 AC: 8332 AN: 49644

Middle Eastern (MID) AF: 0.341 AC: 1889 AN: 5538

European-Non Finnish (NFE) AF: 0.213 AC: 216791 AN: 1019114

Other (OTH) AF: 0.224 AC: 12675 AN: 56474

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

African (AFR) AF: 0.263 AC: 10937 AN: 41510

American (AMR) AF: 0.241 AC: 3682 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.251 AC: 870 AN: 3470

East Asian (EAS) AF: 0.0598 AC: 310 AN: 5184

South Asian (SAS) AF: 0.419 AC: 2020 AN: 4826

European-Finnish (FIN) AF: 0.158 AC: 1678 AN: 10606

Middle Eastern (MID) AF: 0.364 AC: 107 AN: 294

European-Non Finnish (NFE) AF: 0.223 AC: 15185 AN: 67996

Other (OTH) AF: 0.233 AC: 492 AN: 2116

Alfa AF: 0.247 Hom.: 963

Bravo AF: 0.237

Asia WGS AF: 0.242 AC: 842 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.32
DANN	Benign	0.74
PhyloP100		-2.1
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		2.6
Mutation Taster		=100/0	polymorphism (auto)

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