4-25673377-C-G

Variant names:

• chr4-25673377-C-G
• rs2240995
• NM_006424.3:c.1216+123C>G

Variant summary

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

The NM_006424.3(SLC34A2):​c.1216+123C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.209 in 977,658 control chromosomes in the GnomAD database, including 25,500 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 0.18 (3333 hom., cov: 32)
  • Exomes 𝑓: 0.21 (22167 hom.)
• Consequence: SLC34A2 NM_006424.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.21

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=-0.94).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.44 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC34A2	NM_006424.3	c.1216+123C>G		intron_variant	Intron 10 of 12	ENST00000382051.8	NP_006415.3
SLC34A2	NM_001177998.2	c.1213+123C>G		intron_variant	Intron 10 of 12		NP_001171469.2
SLC34A2	NM_001177999.2	c.1213+123C>G		intron_variant	Intron 10 of 12		NP_001171470.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC34A2	ENST00000382051.8	c.1216+123C>G		intron_variant	Intron 10 of 12	1	NM_006424.3	ENSP00000371483.3
SLC34A2	ENST00000503434.5	c.1213+123C>G		intron_variant	Intron 10 of 12	1		ENSP00000423021.1
SLC34A2	ENST00000504570.5	c.1213+123C>G		intron_variant	Intron 10 of 12	1		ENSP00000425501.1
SLC34A2	ENST00000645788.1	c.1213+123C>G		intron_variant	Intron 10 of 12			ENSP00000494094.1

Frequencies

GnomAD3 genomes AF: 0.182 AC: 27581 AN: 151898 Hom.: 3327 Cov.: 32

Gnomad AFR AF: 0.0602

Gnomad AMI AF: 0.209

Gnomad AMR AF: 0.300

Gnomad ASJ AF: 0.167

Gnomad EAS AF: 0.455

Gnomad SAS AF: 0.332

Gnomad FIN AF: 0.291

Gnomad MID AF: 0.204

Gnomad NFE AF: 0.180

Gnomad OTH AF: 0.192

GnomAD4 exome AF: 0.214 AC: 176831 AN: 825642 Hom.: 22167 AF XY: 0.218 AC XY: 93752 AN XY: 429372

Gnomad4 AFR exome AF: 0.0578

Gnomad4 AMR exome AF: 0.326

Gnomad4 ASJ exome AF: 0.178

Gnomad4 EAS exome AF: 0.479

Gnomad4 SAS exome AF: 0.328

Gnomad4 FIN exome AF: 0.295

Gnomad4 NFE exome AF: 0.179

Gnomad4 OTH exome AF: 0.209

GnomAD4 genome AF: 0.181 AC: 27586 AN: 152016 Hom.: 3333 Cov.: 32 AF XY: 0.194 AC XY: 14429 AN XY: 74262

Gnomad4 AFR AF: 0.0601

Gnomad4 AMR AF: 0.300

Gnomad4 ASJ AF: 0.167

Gnomad4 EAS AF: 0.455

Gnomad4 SAS AF: 0.332

Gnomad4 FIN AF: 0.291

Gnomad4 NFE AF: 0.181

Gnomad4 OTH AF: 0.192

Alfa AF: 0.0943 Hom.: 151

Bravo AF: 0.175

Asia WGS AF: 0.346 AC: 1198 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.26
DANN	Benign	0.74

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: rs2240995; hg19: chr4-25674999;