chr11-62876882-G-A

Variant names:

• chr11-62876882-G-A
• rs116133114
• ENST00000377890.6:c.299-4137G>A

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

The NM_001012662.3(SLC3A2):​c.301+3G>A variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00224 in 1,037,170 control chromosomes in the GnomAD database, including 37 homozygotes. In-silico tool predicts a benign outcome for this variant. 2/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.010 (18 hom., cov: 32)
  • Exomes 𝑓: 0.00086 (19 hom.)
• Consequence: SLC3A2 NM_001012662.3 splice_region, intron
• Scores: Splicing: ADA: 0.00002236
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.162
• Publications: 0 publications found

Genes affected

SLC3A2 (HGNC:11026): (solute carrier family 3 member 2) This gene is a member of the solute carrier family and encodes a cell surface, transmembrane protein. The protein exists as the heavy chain of a heterodimer, covalently bound through di-sulfide bonds to one of several possible light chains. The encoded transporter plays a role in regulation of intracellular calcium levels and transports L-type amino acids. Alternatively spliced transcript variants, encoding different isoforms, have been characterized. [provided by RefSeq, Nov 2010]

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BP6: Variant 11-62876882-G-A is Benign according to our data. Variant chr11-62876882-G-A is described in ClinVar as Benign. ClinVar VariationId is 781000.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.0103 (1565/152240) while in subpopulation AFR AF = 0.0358 (1488/41548). AF 95% confidence interval is 0.0343. There are 18 homozygotes in GnomAd4. There are 717 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High AC in GnomAd4 at 1565 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001012662.3. 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
	SLC3A2	NM_001012662.3		c.301+3G>A		splice_region intron	N/A	NP_001012680.1	P08195-5
	SLC3A2	NM_002394.6		c.299-4137G>A		intron	N/A	NP_002385.3
	SLC3A2	NM_001012664.3		c.113-4137G>A		intron	N/A	NP_001012682.1	P08195-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC3A2	ENST00000377890.6	TSL:1	c.299-4137G>A		intron	N/A	ENSP00000367122.2	P08195-1
	SLC3A2	ENST00000377889.6	TSL:1	c.113-4137G>A		intron	N/A	ENSP00000367121.2	P08195-3
	SLC3A2	ENST00000538084.2	TSL:3	c.391+3G>A		splice_region intron	N/A	ENSP00000440001.2	P08195-4

Frequencies

GnomAD3 genomes AF: 0.0103 AC: 1566 AN: 152122 Hom.: 18 Cov.: 32

Gnomad AFR AF: 0.0359

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00354

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.0000944

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.000118

Gnomad OTH AF: 0.00574

GnomAD2 exomes AF: 0.000641 AC: 9 AN: 14030 AF XY: 0.000560

Gnomad AFR exome AF: 0.0385

Gnomad AMR exome AF: 0.000850

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00281

GnomAD4 exome AF: 0.000861 AC: 762 AN: 884930 Hom.: 19 Cov.: 21 AF XY: 0.000728 AC XY: 304 AN XY: 417442

African (AFR) AF: 0.0418 AC: 686 AN: 16402

American (AMR) AF: 0.000302 AC: 1 AN: 3316

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 7256

East Asian (EAS) AF: 0.00 AC: 0 AN: 3954

South Asian (SAS) AF: 0.0000930 AC: 3 AN: 32262

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 4466

Middle Eastern (MID) AF: 0.00145 AC: 5 AN: 3452

European-Non Finnish (NFE) AF: 0.00000765 AC: 6 AN: 784378

Other (OTH) AF: 0.00207 AC: 61 AN: 29444

GnomAD4 genome AF: 0.0103 AC: 1565 AN: 152240 Hom.: 18 Cov.: 32 AF XY: 0.00963 AC XY: 717 AN XY: 74428

African (AFR) AF: 0.0358 AC: 1488 AN: 41548

American (AMR) AF: 0.00354 AC: 54 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5184

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4828

European-Finnish (FIN) AF: 0.0000944 AC: 1 AN: 10588

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.000118 AC: 8 AN: 68028

Other (OTH) AF: 0.00568 AC: 12 AN: 2114

Alfa AF: 0.00544 Hom.: 2

Bravo AF: 0.0121

Asia WGS AF: 0.00231 AC: 8 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	6.1
DANN	Benign	0.31
PhyloP100		0.16
Mutation Taster		=96/4	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.000022
dbscSNV1_RF	Benign	0.0020
SpliceAI score (max)		0.22		Details are displayed if max score is > 0.2
DS_DG_spliceai		0.22		Position offset: -3

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs116133114; hg19: chr11-62644354;