chr19-14971600-G-C

Variant names:

• chr19-14971600-G-C
• rs2285980
• NM_005071.3:c.343+137C>G

Variant summary

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

The NM_005071.3(SLC1A6):​c.343+137C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.542 in 846,028 control chromosomes in the GnomAD database, including 125,727 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 0.53 (21830 hom., cov: 31)
  • Exomes 𝑓: 0.54 (103897 hom.)
• Consequence: SLC1A6 NM_005071.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.103
• Publications: 2 publications found

Genes affected

SLC1A6 (HGNC:10944): (solute carrier family 1 member 6) Predicted to enable high-affinity glutamate transmembrane transporter activity. Involved in neurotransmitter uptake. Located in intermediate filament cytoskeleton and plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.665 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC1A6	NM_005071.3	c.343+137C>G		intron_variant	Intron 3 of 9	ENST00000594383.2	NP_005062.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC1A6	ENST00000594383.2	c.343+137C>G		intron_variant	Intron 3 of 9	2	NM_005071.3	ENSP00000472133.2

Frequencies

GnomAD3 genomes AF: 0.533 AC: 80908 AN: 151860 Hom.: 21819 Cov.: 31

Gnomad AFR AF: 0.508

Gnomad AMI AF: 0.481

Gnomad AMR AF: 0.556

Gnomad ASJ AF: 0.384

Gnomad EAS AF: 0.684

Gnomad SAS AF: 0.630

Gnomad FIN AF: 0.583

Gnomad MID AF: 0.389

Gnomad NFE AF: 0.526

Gnomad OTH AF: 0.496

GnomAD4 exome AF: 0.544 AC: 377340 AN: 694050 Hom.: 103897 AF XY: 0.545 AC XY: 194731 AN XY: 357072

African (AFR) AF: 0.508 AC: 8952 AN: 17614

American (AMR) AF: 0.566 AC: 13217 AN: 23358

Ashkenazi Jewish (ASJ) AF: 0.383 AC: 5954 AN: 15550

East Asian (EAS) AF: 0.685 AC: 22895 AN: 33408

South Asian (SAS) AF: 0.605 AC: 32355 AN: 53452

European-Finnish (FIN) AF: 0.576 AC: 20187 AN: 35076

Middle Eastern (MID) AF: 0.380 AC: 931 AN: 2452

European-Non Finnish (NFE) AF: 0.532 AC: 254804 AN: 478896

Other (OTH) AF: 0.527 AC: 18045 AN: 34244

GnomAD4 genome AF: 0.533 AC: 80958 AN: 151978 Hom.: 21830 Cov.: 31 AF XY: 0.539 AC XY: 40050 AN XY: 74280

African (AFR) AF: 0.508 AC: 21056 AN: 41414

American (AMR) AF: 0.556 AC: 8490 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.384 AC: 1331 AN: 3468

East Asian (EAS) AF: 0.684 AC: 3536 AN: 5170

South Asian (SAS) AF: 0.630 AC: 3033 AN: 4816

European-Finnish (FIN) AF: 0.583 AC: 6167 AN: 10572

Middle Eastern (MID) AF: 0.384 AC: 113 AN: 294

European-Non Finnish (NFE) AF: 0.526 AC: 35752 AN: 67960

Other (OTH) AF: 0.493 AC: 1041 AN: 2112

Alfa AF: 0.346 Hom.: 738

Bravo AF: 0.528

Asia WGS AF: 0.653 AC: 2271 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	1.0
DANN	Benign	0.59
PhyloP100		-0.10
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: rs2285980; hg19: chr19-15082412;