rs12505556

Positions:

• chr4-25675360-C-A
• chr4-25675360-C-G

Variant summary

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

The NM_006424.3(SLC34A2):​c.1458+731C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.157 in 152,228 control chromosomes in the GnomAD database, including 2,520 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 0.16 (2520 hom., cov: 33)
• Consequence: SLC34A2 NM_006424.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.358

Genes affected

SLC34A2 (HGNC:11020): (solute carrier family 34 member 2) The protein encoded by this gene is a pH-sensitive sodium-dependent phosphate transporter. Phosphate uptake is increased at lower pH. Defects in this gene are a cause of pulmonary alveolar microlithiasis. Three transcript variants encoding two different isoforms have been found for this gene. [provided by RefSeq, May 2010]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.555 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLC34A2	NM_006424.3	c.1458+731C>A		intron_variant		ENST00000382051.8	NP_006415.3
SLC34A2	NM_001177998.2	c.1455+731C>A		intron_variant			NP_001171469.2
SLC34A2	NM_001177999.2	c.1455+731C>A		intron_variant			NP_001171470.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLC34A2	ENST00000382051.8	c.1458+731C>A		intron_variant		1	NM_006424.3	ENSP00000371483	P4
SLC34A2	ENST00000503434.5	c.1455+731C>A		intron_variant		1		ENSP00000423021	A2
SLC34A2	ENST00000504570.5	c.1455+731C>A		intron_variant		1		ENSP00000425501	A2
SLC34A2	ENST00000645788.1	c.1455+731C>A		intron_variant				ENSP00000494094	A2

Frequencies

GnomAD3 genomes AF: 0.157 AC: 23906 AN: 152110 Hom.: 2514 Cov.: 33

Gnomad AFR AF: 0.136

Gnomad AMI AF: 0.178

Gnomad AMR AF: 0.229

Gnomad ASJ AF: 0.175

Gnomad EAS AF: 0.572

Gnomad SAS AF: 0.169

Gnomad FIN AF: 0.151

Gnomad MID AF: 0.139

Gnomad NFE AF: 0.121

Gnomad OTH AF: 0.171

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

GnomAD4 genome AF: 0.157 AC: 23930 AN: 152228 Hom.: 2520 Cov.: 33 AF XY: 0.162 AC XY: 12095 AN XY: 74436

Gnomad4 AFR AF: 0.136

Gnomad4 AMR AF: 0.230

Gnomad4 ASJ AF: 0.175

Gnomad4 EAS AF: 0.572

Gnomad4 SAS AF: 0.168

Gnomad4 FIN AF: 0.151

Gnomad4 NFE AF: 0.121

Gnomad4 OTH AF: 0.171

Alfa AF: 0.133 Hom.: 2099

Bravo AF: 0.169

Asia WGS AF: 0.362 AC: 1257 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	2.5
DANN	Benign	0.80

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: rs12505556; hg19: chr4-25676982;