NM_018018.5:c.-112-294C>T

Variant names:

• chr12-46793477-G-A
• rs180438
• NM_018018.5:c.-112-294C>T

Variant summary

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

The NM_018018.5(SLC38A4):​c.-112-294C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.621 in 151,988 control chromosomes in the GnomAD database, including 33,919 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 0.62 (33919 hom., cov: 32)
• Consequence: SLC38A4 NM_018018.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.860
• Publications: 8 publications found

Genes affected

SLC38A4 (HGNC:14679): (solute carrier family 38 member 4) SLC38A4 is found predominantly in liver and transports both cationic and neutral amino acids. The transport of cationic amino acids by SLC38A4 is Na(+) and pH independent, while the transport of neutral amino acids is Na(+) and pH dependent (Hatanaka et al., 2001 [PubMed 11342143]).[supplied by OMIM, Mar 2008]

SLC38A4-AS1 (HGNC:56178): (SLC38A4 antisense RNA 1)

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.798 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_018018.5. 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
	SLC38A4	NM_018018.5	MANE Select	c.-112-294C>T		intron	N/A	NP_060488.2
	SLC38A4	NM_001143824.2		c.-112-294C>T		intron	N/A	NP_001137296.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC38A4	ENST00000266579.9	TSL:1 MANE Select	c.-112-294C>T		intron	N/A	ENSP00000266579.4
	SLC38A4	ENST00000447411.5	TSL:1	c.-112-294C>T		intron	N/A	ENSP00000389843.1
	SLC38A4-AS1	ENST00000611243.2	TSL:1	n.360-81340G>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.622 AC: 94417 AN: 151870 Hom.: 33925 Cov.: 32

Gnomad AFR AF: 0.240

Gnomad AMI AF: 0.834

Gnomad AMR AF: 0.667

Gnomad ASJ AF: 0.813

Gnomad EAS AF: 0.574

Gnomad SAS AF: 0.579

Gnomad FIN AF: 0.823

Gnomad MID AF: 0.728

Gnomad NFE AF: 0.804

Gnomad OTH AF: 0.692

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

GnomAD4 genome AF: 0.621 AC: 94418 AN: 151988 Hom.: 33919 Cov.: 32 AF XY: 0.623 AC XY: 46262 AN XY: 74292

African (AFR) AF: 0.240 AC: 9942 AN: 41460

American (AMR) AF: 0.667 AC: 10170 AN: 15244

Ashkenazi Jewish (ASJ) AF: 0.813 AC: 2823 AN: 3472

East Asian (EAS) AF: 0.574 AC: 2955 AN: 5144

South Asian (SAS) AF: 0.578 AC: 2786 AN: 4816

European-Finnish (FIN) AF: 0.823 AC: 8699 AN: 10574

Middle Eastern (MID) AF: 0.738 AC: 217 AN: 294

European-Non Finnish (NFE) AF: 0.804 AC: 54613 AN: 67958

Other (OTH) AF: 0.687 AC: 1454 AN: 2116

Alfa AF: 0.771 Hom.: 126002

Bravo AF: 0.596

Asia WGS AF: 0.572 AC: 1989 AN: 3470

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	9.2
DANN	Benign	0.72
PhyloP100		-0.86
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: rs180438; hg19: chr12-47187260;