NM_012244.4:c.509-4781C>G

Variant names:

• chr14-23147985-G-C
• rs12588118
• NM_012244.4:c.509-4781C>G

Variant summary

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

The NM_012244.4(SLC7A8):​c.509-4781C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.806 in 152,088 control chromosomes in the GnomAD database, including 49,538 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 0.81 (49538 hom., cov: 31)
• Consequence: SLC7A8 NM_012244.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.11
• Publications: 6 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]

ENSG00000295903 (HGNC:):

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 (EAS) allele frequency at 95% confidence interval = 0.884 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC7A8	NM_012244.4	MANE Select	c.509-4781C>G		intron	N/A	NP_036376.2
	SLC7A8	NM_001267036.1		c.194-4781C>G		intron	N/A	NP_001253965.1
	SLC7A8	NM_182728.3		c.-101-4781C>G		intron	N/A	NP_877392.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC7A8	ENST00000316902.12	TSL:1 MANE Select	c.509-4781C>G		intron	N/A	ENSP00000320378.7
	SLC7A8	ENST00000453702.5	TSL:1	c.-101-4781C>G		intron	N/A	ENSP00000391577.1
	SLC7A8	ENST00000469263.5	TSL:1	c.509-4781C>G		intron	N/A	ENSP00000435114.1

Frequencies

GnomAD3 genomes AF: 0.806 AC: 122441 AN: 151970 Hom.: 49489 Cov.: 31

Gnomad AFR AF: 0.838

Gnomad AMI AF: 0.836

Gnomad AMR AF: 0.832

Gnomad ASJ AF: 0.791

Gnomad EAS AF: 0.905

Gnomad SAS AF: 0.729

Gnomad FIN AF: 0.799

Gnomad MID AF: 0.769

Gnomad NFE AF: 0.780

Gnomad OTH AF: 0.800

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

GnomAD4 genome AF: 0.806 AC: 122545 AN: 152088 Hom.: 49538 Cov.: 31 AF XY: 0.806 AC XY: 59897 AN XY: 74340

African (AFR) AF: 0.838 AC: 34761 AN: 41498

American (AMR) AF: 0.832 AC: 12715 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.791 AC: 2741 AN: 3466

East Asian (EAS) AF: 0.905 AC: 4665 AN: 5152

South Asian (SAS) AF: 0.729 AC: 3511 AN: 4816

European-Finnish (FIN) AF: 0.799 AC: 8454 AN: 10580

Middle Eastern (MID) AF: 0.762 AC: 224 AN: 294

European-Non Finnish (NFE) AF: 0.780 AC: 53019 AN: 67980

Other (OTH) AF: 0.802 AC: 1693 AN: 2110

Alfa AF: 0.748 Hom.: 2281

Bravo AF: 0.814

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.18
DANN	Benign	0.53
PhyloP100		-1.1
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: rs12588118; hg19: chr14-23617194;