2-44298871-G-A

Variant names:

• chr2-44298871-G-A
• rs2165421
• NM_000341.4:c.892-1100G>A

Variant summary

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

The NM_000341.4(SLC3A1):​c.892-1100G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.606 in 151,816 control chromosomes in the GnomAD database, including 28,341 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 0.61 (28341 hom., cov: 30)
• Consequence: SLC3A1 NM_000341.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.167
• Publications: 1 publications found

Genes affected

SLC3A1 (HGNC:11025): (solute carrier family 3 member 1) This gene encodes a type II membrane glycoprotein which is one of the components of the renal amino acid transporter which transports neutral and basic amino acids in the renal tubule and intestinal tract. Mutations and deletions in this gene are associated with cystinuria. Alternatively spliced transcript variants have been described, but their biological validity has not been determined. [provided by RefSeq, Jul 2008]

SLC3A1 Gene-Disease associations (from GenCC):

• cystinuria

  Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae), ClinGen
• cystinuria type A

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ENSG00000285542 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.657 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000341.4. 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
	SLC3A1	NM_000341.4	MANE Select	c.892-1100G>A		intron	N/A	NP_000332.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC3A1	ENST00000260649.11	TSL:1 MANE Select	c.892-1100G>A		intron	N/A	ENSP00000260649.6
	SLC3A1	ENST00000409229.7	TSL:1	c.892-1100G>A		intron	N/A	ENSP00000386620.3
	SLC3A1	ENST00000409387.5	TSL:1	c.892-1100G>A		intron	N/A	ENSP00000387308.1

Frequencies

GnomAD3 genomes AF: 0.606 AC: 91923 AN: 151696 Hom.: 28345 Cov.: 30

Gnomad AFR AF: 0.560

Gnomad AMI AF: 0.719

Gnomad AMR AF: 0.580

Gnomad ASJ AF: 0.657

Gnomad EAS AF: 0.304

Gnomad SAS AF: 0.614

Gnomad FIN AF: 0.577

Gnomad MID AF: 0.633

Gnomad NFE AF: 0.662

Gnomad OTH AF: 0.613

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

GnomAD4 genome AF: 0.606 AC: 91949 AN: 151816 Hom.: 28341 Cov.: 30 AF XY: 0.598 AC XY: 44389 AN XY: 74188

African (AFR) AF: 0.560 AC: 23149 AN: 41368

American (AMR) AF: 0.579 AC: 8845 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.657 AC: 2281 AN: 3470

East Asian (EAS) AF: 0.304 AC: 1565 AN: 5156

South Asian (SAS) AF: 0.615 AC: 2967 AN: 4826

European-Finnish (FIN) AF: 0.577 AC: 6064 AN: 10506

Middle Eastern (MID) AF: 0.633 AC: 186 AN: 294

European-Non Finnish (NFE) AF: 0.662 AC: 44958 AN: 67908

Other (OTH) AF: 0.607 AC: 1280 AN: 2108

Alfa AF: 0.650 Hom.: 15315

Bravo AF: 0.600

Asia WGS AF: 0.478 AC: 1667 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	1.4
DANN	Benign	0.34
PhyloP100		0.17
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: rs2165421; hg19: chr2-44526010;