14-23167883-C-T

Variant names:

• chr14-23167883-C-T
• rs2268875
• NM_012244.4:c.152-1343G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_012244.4(SLC7A8):​c.152-1343G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.23 in 151,974 control chromosomes in the GnomAD database, including 4,567 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 (4567 hom., cov: 32)
• Consequence: SLC7A8 NM_012244.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.399
• Publications: 3 publications found

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

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.435 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_012244.4. 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
	SLC7A8	NM_012244.4	MANE Select	c.152-1343G>A		intron	N/A	NP_036376.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC7A8	ENST00000316902.12	TSL:1 MANE Select	c.152-1343G>A		intron	N/A	ENSP00000320378.7	Q9UHI5-1
	SLC7A8	ENST00000469263.5	TSL:1	c.152-1343G>A		intron	N/A	ENSP00000435114.1	E9PLV9
	SLC7A8	ENST00000524758.1	TSL:4	c.152-1343G>A		intron	N/A	ENSP00000434352.1	E9PQT4

Frequencies

GnomAD3 genomes AF: 0.229 AC: 34814 AN: 151854 Hom.: 4545 Cov.: 32

Gnomad AFR AF: 0.334

Gnomad AMI AF: 0.105

Gnomad AMR AF: 0.153

Gnomad ASJ AF: 0.200

Gnomad EAS AF: 0.450

Gnomad SAS AF: 0.235

Gnomad FIN AF: 0.156

Gnomad MID AF: 0.188

Gnomad NFE AF: 0.181

Gnomad OTH AF: 0.209

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

GnomAD4 genome AF: 0.230 AC: 34890 AN: 151974 Hom.: 4567 Cov.: 32 AF XY: 0.228 AC XY: 16932 AN XY: 74266

African (AFR) AF: 0.334 AC: 13833 AN: 41444

American (AMR) AF: 0.153 AC: 2339 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.200 AC: 694 AN: 3468

East Asian (EAS) AF: 0.451 AC: 2312 AN: 5130

South Asian (SAS) AF: 0.235 AC: 1134 AN: 4816

European-Finnish (FIN) AF: 0.156 AC: 1649 AN: 10558

Middle Eastern (MID) AF: 0.182 AC: 53 AN: 292

European-Non Finnish (NFE) AF: 0.181 AC: 12315 AN: 67968

Other (OTH) AF: 0.220 AC: 465 AN: 2114

Alfa AF: 0.194 Hom.: 5727

Bravo AF: 0.236

Asia WGS AF: 0.334 AC: 1160 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.64
DANN	Benign	0.55
PhyloP100		-0.40
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: rs2268875; hg19: chr14-23637092;