19-49441627-C-G

Variant names:

• chr19-49441627-C-G
• rs74174284
• ENST00000600601.5:c.-140+651G>C

Variant summary

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

The ENST00000600601.5(SLC17A7):​c.-140+651G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.356 in 200,084 control chromosomes in the GnomAD database, including 14,421 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 0.34 (9622 hom., cov: 21)
  • Exomes 𝑓: 0.41 (4799 hom.)
• Consequence: SLC17A7 ENST00000600601.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.439
• Publications: 7 publications found

Genes affected

SLC17A7 (HGNC:16704): (solute carrier family 17 member 7) The protein encoded by this gene is a vesicle-bound, sodium-dependent phosphate transporter that is specifically expressed in the neuron-rich regions of the brain. It is preferentially associated with the membranes of synaptic vesicles and functions in glutamate transport. The protein shares 82% identity with the differentiation-associated Na-dependent inorganic phosphate cotransporter and they appear to form a distinct class within the Na+/Pi cotransporter family. [provided by RefSeq, Jul 2008]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.55).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.471 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000600601.5. 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
	SLC17A7	NM_020309.4	MANE Select	c.-248G>C		upstream_gene	N/A	NP_064705.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC17A7	ENST00000600601.5	TSL:2	c.-140+651G>C		intron	N/A	ENSP00000470338.1
	SLC17A7	ENST00000221485.8	TSL:1 MANE Select	c.-248G>C		upstream_gene	N/A	ENSP00000221485.2

Frequencies

GnomAD3 genomes AF: 0.337 AC: 48777 AN: 144700 Hom.: 9617 Cov.: 21

Gnomad AFR AF: 0.155

Gnomad AMI AF: 0.296

Gnomad AMR AF: 0.281

Gnomad ASJ AF: 0.493

Gnomad EAS AF: 0.300

Gnomad SAS AF: 0.487

Gnomad FIN AF: 0.413

Gnomad MID AF: 0.455

Gnomad NFE AF: 0.431

Gnomad OTH AF: 0.339

GnomAD4 exome AF: 0.406 AC: 22425 AN: 55274 Hom.: 4799 AF XY: 0.413 AC XY: 11730 AN XY: 28398

African (AFR) AF: 0.131 AC: 139 AN: 1062

American (AMR) AF: 0.257 AC: 145 AN: 564

Ashkenazi Jewish (ASJ) AF: 0.502 AC: 281 AN: 560

East Asian (EAS) AF: 0.266 AC: 181 AN: 680

South Asian (SAS) AF: 0.471 AC: 468 AN: 994

European-Finnish (FIN) AF: 0.439 AC: 807 AN: 1840

Middle Eastern (MID) AF: 0.577 AC: 90 AN: 156

European-Non Finnish (NFE) AF: 0.413 AC: 19510 AN: 47222

Other (OTH) AF: 0.366 AC: 804 AN: 2196

GnomAD4 genome AF: 0.337 AC: 48810 AN: 144810 Hom.: 9622 Cov.: 21 AF XY: 0.338 AC XY: 23800 AN XY: 70516

African (AFR) AF: 0.155 AC: 6077 AN: 39136

American (AMR) AF: 0.281 AC: 4159 AN: 14812

Ashkenazi Jewish (ASJ) AF: 0.493 AC: 1690 AN: 3426

East Asian (EAS) AF: 0.300 AC: 1456 AN: 4856

South Asian (SAS) AF: 0.488 AC: 2217 AN: 4542

European-Finnish (FIN) AF: 0.413 AC: 3856 AN: 9334

Middle Eastern (MID) AF: 0.455 AC: 131 AN: 288

European-Non Finnish (NFE) AF: 0.431 AC: 28277 AN: 65536

Other (OTH) AF: 0.343 AC: 688 AN: 2004

Alfa AF: 0.255 Hom.: 736

Bravo AF: 0.314

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.55
CADD	Benign	14
DANN	Benign	0.63
PhyloP100		0.44
PromoterAI		-0.070	Neutral
Mutation Taster		=100/0	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs74174284; hg19: chr19-49944884;