ENST00000377890.6:c.299-4137G>A

Variant names:

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

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

The ENST00000377890.6(SLC3A2):​c.299-4137G>A variant causes a 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. 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 ENST00000377890.6 intron
• Scores: Splicing: ADA: 0.00002236
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.162

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

Verdict is Benign. Variant got -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 id 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 male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High AC in GnomAd4 at 1565 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC3A2	NM_001012662.3	c.301+3G>A		splice_region_variant, intron_variant	Intron 3 of 11		NP_001012680.1
SLC3A2	NM_002394.6	c.299-4137G>A		intron_variant	Intron 3 of 11		NP_002385.3
SLC3A2	NM_001012664.3	c.113-4137G>A		intron_variant	Intron 1 of 9		NP_001012682.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC3A2	ENST00000377890.6	c.299-4137G>A		intron_variant	Intron 3 of 11	1		ENSP00000367122.2
SLC3A2	ENST00000377889.6	c.113-4137G>A		intron_variant	Intron 1 of 9	1		ENSP00000367121.2
SLC3A2	ENST00000538084.2	c.391+3G>A		splice_region_variant, intron_variant	Intron 4 of 12	3		ENSP00000440001.2

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

GnomAD3 exomes AF: 0.000641 AC: 9 AN: 14030 Hom.: 1 AF XY: 0.000560 AC XY: 5 AN XY: 8930

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 SAS exome AF: 0.000675

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

Gnomad4 AFR exome AF: 0.0418

Gnomad4 AMR exome AF: 0.000302

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000930

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000765

Gnomad4 OTH exome AF: 0.00207

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

Gnomad4 AFR AF: 0.0358

Gnomad4 AMR AF: 0.00354

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000207

Gnomad4 FIN AF: 0.0000944

Gnomad4 NFE AF: 0.000118

Gnomad4 OTH AF: 0.00568

Alfa AF: 0.00472 Hom.: 1

Bravo AF: 0.0121

Asia WGS AF: 0.00231 AC: 8 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Dec 31, 2019

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	6.1
DANN	Benign	0.31

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

Publications

LitVar

Other links and lift over

dbSNP: rs116133114; hg19: chr11-62644354;