rs4764738

Variant names:

• chr12-100378452-G-A
• rs4764738
• NM_139319.3:c.102-2249G>A

Your query was ambiguous. Multiple possible variants found:

• chr12-100378452-G-A
• chr12-100378452-G-C
• chr12-100378452-G-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_139319.3(SLC17A8):​c.102-2249G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.543 in 151,754 control chromosomes in the GnomAD database, including 22,957 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 0.54 (22957 hom., cov: 30)
• Consequence: SLC17A8 NM_139319.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.58

Genes affected

SLC17A8 (HGNC:20151): (solute carrier family 17 member 8) This gene encodes a vesicular glutamate transporter. The encoded protein transports the neurotransmitter glutamate into synaptic vesicles before it is released into the synaptic cleft. Mutations in this gene are the cause of autosomal-dominant nonsyndromic type 25 deafness. Alternate splicing results in multiple transcript variants.[provided by RefSeq, May 2010]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.846 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC17A8	NM_139319.3	c.102-2249G>A		intron_variant	Intron 1 of 11	ENST00000323346.10	NP_647480.1
SLC17A8	NM_001145288.2	c.102-2249G>A		intron_variant	Intron 1 of 10		NP_001138760.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC17A8	ENST00000323346.10	c.102-2249G>A		intron_variant	Intron 1 of 11	1	NM_139319.3	ENSP00000316909.4
SLC17A8	ENST00000392989.3	c.102-2249G>A		intron_variant	Intron 1 of 10	1		ENSP00000376715.3

Frequencies

GnomAD3 genomes AF: 0.543 AC: 82375 AN: 151636 Hom.: 22945 Cov.: 30

Gnomad AFR AF: 0.561

Gnomad AMI AF: 0.464

Gnomad AMR AF: 0.621

Gnomad ASJ AF: 0.505

Gnomad EAS AF: 0.868

Gnomad SAS AF: 0.697

Gnomad FIN AF: 0.536

Gnomad MID AF: 0.519

Gnomad NFE AF: 0.484

Gnomad OTH AF: 0.541

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

GnomAD4 genome AF: 0.543 AC: 82430 AN: 151754 Hom.: 22957 Cov.: 30 AF XY: 0.551 AC XY: 40830 AN XY: 74164

Gnomad4 AFR AF: 0.561

Gnomad4 AMR AF: 0.622

Gnomad4 ASJ AF: 0.505

Gnomad4 EAS AF: 0.867

Gnomad4 SAS AF: 0.696

Gnomad4 FIN AF: 0.536

Gnomad4 NFE AF: 0.484

Gnomad4 OTH AF: 0.539

Alfa AF: 0.519 Hom.: 2570

Bravo AF: 0.551

Asia WGS AF: 0.752 AC: 2615 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	6.0
DANN	Benign	0.45

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: rs4764738; hg19: chr12-100772230;