rs2240996

Positions:

• chr4-25673478-C-A

Variant summary

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

The NM_006424.3(SLC34A2):​c.1216+224C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.214 in 152,046 control chromosomes in the GnomAD database, including 4,965 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 0.21 (4965 hom., cov: 32)
• Consequence: SLC34A2 NM_006424.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.551

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=-0.97).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.43 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLC34A2	NM_006424.3	c.1216+224C>A		intron_variant		ENST00000382051.8
SLC34A2	NM_001177998.2	c.1213+224C>A		intron_variant
SLC34A2	NM_001177999.2	c.1213+224C>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC34A2	ENST00000382051.8	c.1216+224C>A		intron_variant		1	NM_006424.3	P4
SLC34A2	ENST00000503434.5	c.1213+224C>A		intron_variant		1		A2
SLC34A2	ENST00000504570.5	c.1213+224C>A		intron_variant		1		A2
SLC34A2	ENST00000645788.1	c.1213+224C>A		intron_variant				A2

Frequencies

GnomAD3 genomes AF: 0.214 AC: 32532 AN: 151928 Hom.: 4952 Cov.: 32

Gnomad AFR AF: 0.435

Gnomad AMI AF: 0.137

Gnomad AMR AF: 0.208

Gnomad ASJ AF: 0.117

Gnomad EAS AF: 0.252

Gnomad SAS AF: 0.0871

Gnomad FIN AF: 0.0955

Gnomad MID AF: 0.114

Gnomad NFE AF: 0.113

Gnomad OTH AF: 0.191

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

GnomAD4 genome AF: 0.214 AC: 32609 AN: 152046 Hom.: 4965 Cov.: 32 AF XY: 0.213 AC XY: 15868 AN XY: 74346

Gnomad4 AFR AF: 0.435

Gnomad4 AMR AF: 0.209

Gnomad4 ASJ AF: 0.117

Gnomad4 EAS AF: 0.251

Gnomad4 SAS AF: 0.0870

Gnomad4 FIN AF: 0.0955

Gnomad4 NFE AF: 0.113

Gnomad4 OTH AF: 0.193

Alfa AF: 0.184 Hom.: 1247

Bravo AF: 0.233

Asia WGS AF: 0.193 AC: 672 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	0.99
DANN	Benign	0.69

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs2240996; hg19: chr4-25675100;