rs180438

Positions:

• chr12-46793477-G-A
• chr12-46793477-G-C

Variant summary

Our verdict is Benign. Variant got -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

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:):

ACMG classification

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLC38A4	NM_018018.5	c.-112-294C>T		intron_variant		ENST00000266579.9	NP_060488.2
SLC38A4	NM_001143824.2	c.-112-294C>T		intron_variant			NP_001137296.1
SLC38A4	XM_005268997.3	c.-112-294C>T		intron_variant			XP_005269054.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLC38A4	ENST00000266579.9	c.-112-294C>T		intron_variant		1	NM_018018.5	ENSP00000266579.4

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

Gnomad4 AFR AF: 0.240

Gnomad4 AMR AF: 0.667

Gnomad4 ASJ AF: 0.813

Gnomad4 EAS AF: 0.574

Gnomad4 SAS AF: 0.578

Gnomad4 FIN AF: 0.823

Gnomad4 NFE AF: 0.804

Gnomad4 OTH AF: 0.687

Alfa AF: 0.774 Hom.: 88958

Bravo AF: 0.596

Asia WGS AF: 0.572 AC: 1989 AN: 3470

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	9.2
DANN	Benign	0.72

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: rs180438; hg19: chr12-47187260;