rs2268876

Positions:

• chr14-23167749-T-C

Variant summary

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

The NM_012244.4(SLC7A8):​c.152-1209A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.208 in 151,968 control chromosomes in the GnomAD database, including 3,574 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 0.21 (3574 hom., cov: 32)
• Consequence: SLC7A8 NM_012244.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.625

Genes affected

SLC7A8 (HGNC:11066): (solute carrier family 7 member 8) Enables several functions, including neutral amino acid transmembrane transporter activity; thyroid hormone transmembrane transporter activity; and toxin transmembrane transporter activity. Involved in L-alanine import across plasma membrane; L-leucine import across plasma membrane; and thyroid hormone transport. Located in plasma membrane. Part of basolateral 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=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.435 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLC7A8	NM_012244.4	c.152-1209A>G		intron_variant		ENST00000316902.12	NP_036376.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLC7A8	ENST00000316902.12	c.152-1209A>G		intron_variant		1	NM_012244.4	ENSP00000320378	P1
SLC7A8	ENST00000469263.5	c.152-1209A>G		intron_variant		1		ENSP00000435114
SLC7A8	ENST00000524758.1	c.152-1209A>G		intron_variant		4		ENSP00000434352
SLC7A8	ENST00000525062.1	c.152-1209A>G		intron_variant		3		ENSP00000436665

Frequencies

GnomAD3 genomes AF: 0.207 AC: 31498 AN: 151850 Hom.: 3556 Cov.: 32

Gnomad AFR AF: 0.257

Gnomad AMI AF: 0.105

Gnomad AMR AF: 0.144

Gnomad ASJ AF: 0.200

Gnomad EAS AF: 0.449

Gnomad SAS AF: 0.235

Gnomad FIN AF: 0.156

Gnomad MID AF: 0.187

Gnomad NFE AF: 0.181

Gnomad OTH AF: 0.195

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.208 AC: 31567 AN: 151968 Hom.: 3574 Cov.: 32 AF XY: 0.207 AC XY: 15356 AN XY: 74266

Gnomad4 AFR AF: 0.258

Gnomad4 AMR AF: 0.144

Gnomad4 ASJ AF: 0.200

Gnomad4 EAS AF: 0.450

Gnomad4 SAS AF: 0.235

Gnomad4 FIN AF: 0.156

Gnomad4 NFE AF: 0.181

Gnomad4 OTH AF: 0.206

Alfa AF: 0.185 Hom.: 530

Bravo AF: 0.210

Asia WGS AF: 0.328 AC: 1139 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.16
DANN	Benign	0.69

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: rs2268876; hg19: chr14-23636958;