2-112652438-A-G

Variant names:

• chr2-112652438-A-G
• rs10758
• NM_005415.5:c.562-264A>G

Variant summary

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

The NM_005415.5(SLC20A1):​c.562-264A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.312 in 498,412 control chromosomes in the GnomAD database, including 28,795 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 0.30 (7752 hom., cov: 32)
  • Exomes 𝑓: 0.32 (21043 hom.)
• Consequence: SLC20A1 NM_005415.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0320
• Publications: 8 publications found

Genes affected

SLC20A1 (HGNC:10946): (solute carrier family 20 member 1) The protein encoded by this gene is a sodium-phosphate symporter that absorbs phosphate from interstitial fluid for use in cellular functions such as metabolism, signal transduction, and nucleic acid and lipid synthesis. The encoded protein is also a retroviral receptor, causing human cells to be susceptible to infection by gibbon ape leukemia virus, simian sarcoma-associated virus, feline leukemia virus subgroup B, and 10A1 murine leukemia virus.[provided by RefSeq, Mar 2011]

SLC20A1 Gene-Disease associations (from GenCC):

• exstrophy-epispadias complex

  Inheritance: AD Classification: STRONG Submitted by: PanelApp Australia

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.767 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005415.5. 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
	SLC20A1	NM_005415.5	MANE Select	c.562-264A>G		intron	N/A	NP_005406.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC20A1	ENST00000272542.8	TSL:1 MANE Select	c.562-264A>G		intron	N/A	ENSP00000272542.3	Q8WUM9
	SLC20A1	ENST00000922300.1		c.562-264A>G		intron	N/A	ENSP00000592359.1
	SLC20A1	ENST00000922295.1		c.562-264A>G		intron	N/A	ENSP00000592354.1

Frequencies

GnomAD3 genomes AF: 0.301 AC: 45676 AN: 151876 Hom.: 7748 Cov.: 32

Gnomad AFR AF: 0.261

Gnomad AMI AF: 0.344

Gnomad AMR AF: 0.372

Gnomad ASJ AF: 0.345

Gnomad EAS AF: 0.787

Gnomad SAS AF: 0.378

Gnomad FIN AF: 0.306

Gnomad MID AF: 0.329

Gnomad NFE AF: 0.262

Gnomad OTH AF: 0.304

GnomAD4 exome AF: 0.316 AC: 109606 AN: 346420 Hom.: 21043 Cov.: 0 AF XY: 0.318 AC XY: 58229 AN XY: 183058

African (AFR) AF: 0.259 AC: 2632 AN: 10154

American (AMR) AF: 0.383 AC: 4685 AN: 12232

Ashkenazi Jewish (ASJ) AF: 0.332 AC: 3674 AN: 11058

East Asian (EAS) AF: 0.798 AC: 18509 AN: 23204

South Asian (SAS) AF: 0.348 AC: 12315 AN: 35410

European-Finnish (FIN) AF: 0.297 AC: 6078 AN: 20484

Middle Eastern (MID) AF: 0.271 AC: 411 AN: 1514

European-Non Finnish (NFE) AF: 0.260 AC: 55210 AN: 212108

Other (OTH) AF: 0.301 AC: 6092 AN: 20256

GnomAD4 genome AF: 0.301 AC: 45697 AN: 151992 Hom.: 7752 Cov.: 32 AF XY: 0.307 AC XY: 22772 AN XY: 74280

African (AFR) AF: 0.261 AC: 10817 AN: 41446

American (AMR) AF: 0.373 AC: 5696 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.345 AC: 1198 AN: 3472

East Asian (EAS) AF: 0.787 AC: 4067 AN: 5166

South Asian (SAS) AF: 0.378 AC: 1816 AN: 4808

European-Finnish (FIN) AF: 0.306 AC: 3218 AN: 10526

Middle Eastern (MID) AF: 0.330 AC: 97 AN: 294

European-Non Finnish (NFE) AF: 0.262 AC: 17838 AN: 67984

Other (OTH) AF: 0.301 AC: 636 AN: 2112

Alfa AF: 0.274 Hom.: 15226

Bravo AF: 0.301

Asia WGS AF: 0.535 AC: 1860 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	1.7
DANN	Benign	0.53
PhyloP100		0.032
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: rs10758; hg19: chr2-113410015;