6-25771819-A-G

Variant names:

• chr6-25771819-A-G
• rs4712972
• NM_005495.3:c.706+807A>G

Variant summary

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

The NM_005495.3(SLC17A4):​c.706+807A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.78 in 151,990 control chromosomes in the GnomAD database, including 48,145 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 0.78 (48145 hom., cov: 30)
• Consequence: SLC17A4 NM_005495.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.15
• Publications: 37 publications found

Genes affected

SLC17A4 (HGNC:10932): (solute carrier family 17 member 4) Phosphate homeostasis is maintained by regulating intake, intestinal absorption, bone deposition and resorption, and renal excretion of phosphate. The central molecule in the control of phosphate excretion from the kidney is the sodium/phosphate cotransporter NPT1 (SLC17A1; MIM 182308), which is located in the renal proximal tubule. NPT1 uses the transmembrane electrochemical potential gradient of sodium to transport phosphate across the cell membrane. SLC17A4 is a similar sodium/phosphate cotransporter in the intestinal mucosa that plays an important role in the absorption of phosphate from the intestine (summary by Shibui et al., 1999 [PubMed 10319585]).[supplied by OMIM, Feb 2011]

SLC17A1 (HGNC:10929): (solute carrier family 17 member 1) Predicted to enable sialic acid transmembrane transporter activity. Involved in urate metabolic process and urate transport. Located in apical 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=-0.97).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.929 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005495.3. 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
	SLC17A4	NM_005495.3	MANE Select	c.706+807A>G		intron	N/A	NP_005486.1	Q9Y2C5-1
	SLC17A4	NM_001286121.1		c.544+807A>G		intron	N/A	NP_001273050.1	Q9Y2C5-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC17A4	ENST00000377905.9	TSL:1 MANE Select	c.706+807A>G		intron	N/A	ENSP00000367137.4	Q9Y2C5-1
	SLC17A4	ENST00000867588.1		c.706+807A>G		intron	N/A	ENSP00000537647.1
	SLC17A4	ENST00000867590.1		c.706+807A>G		intron	N/A	ENSP00000537649.1

Frequencies

GnomAD3 genomes AF: 0.780 AC: 118421 AN: 151872 Hom.: 48110 Cov.: 30

Gnomad AFR AF: 0.528

Gnomad AMI AF: 0.979

Gnomad AMR AF: 0.835

Gnomad ASJ AF: 0.832

Gnomad EAS AF: 0.951

Gnomad SAS AF: 0.935

Gnomad FIN AF: 0.924

Gnomad MID AF: 0.753

Gnomad NFE AF: 0.869

Gnomad OTH AF: 0.769

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

GnomAD4 genome AF: 0.780 AC: 118505 AN: 151990 Hom.: 48145 Cov.: 30 AF XY: 0.788 AC XY: 58487 AN XY: 74268

African (AFR) AF: 0.528 AC: 21845 AN: 41394

American (AMR) AF: 0.836 AC: 12756 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.832 AC: 2887 AN: 3470

East Asian (EAS) AF: 0.952 AC: 4903 AN: 5152

South Asian (SAS) AF: 0.936 AC: 4503 AN: 4810

European-Finnish (FIN) AF: 0.924 AC: 9785 AN: 10594

Middle Eastern (MID) AF: 0.762 AC: 224 AN: 294

European-Non Finnish (NFE) AF: 0.869 AC: 59081 AN: 67988

Other (OTH) AF: 0.772 AC: 1628 AN: 2110

Alfa AF: 0.833 Hom.: 167759

Bravo AF: 0.760

Asia WGS AF: 0.911 AC: 3167 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	0.30
DANN	Benign	0.64
PhyloP100		-1.1
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: rs4712972; hg19: chr6-25772047;