chr4-25657986-T-C

Variant names:

• chr4-25657986-T-C
• rs12501856
• NM_006424.3:c.-4+2096T>C

Variant summary

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

The NM_006424.3(SLC34A2):​c.-4+2096T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.265 in 152,104 control chromosomes in the GnomAD database, including 6,586 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 0.27 (6586 hom., cov: 32)
• Consequence: SLC34A2 NM_006424.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.04
• Publications: 4 publications found

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]

SLC34A2 Gene-Disease associations (from GenCC):

• pulmonary alveolar microlithiasis

  Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae), PanelApp Australia, Orphanet

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.344 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006424.3. 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
	SLC34A2	NM_006424.3	MANE Select	c.-4+2096T>C		intron	N/A	NP_006415.3	O95436-1
	SLC34A2	NM_001177998.2		c.-4+2096T>C		intron	N/A	NP_001171469.2	O95436-2
	SLC34A2	NM_001177999.2		c.-4+1422T>C		intron	N/A	NP_001171470.2	O95436-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC34A2	ENST00000382051.8	TSL:1 MANE Select	c.-4+2096T>C		intron	N/A	ENSP00000371483.3	O95436-1
	SLC34A2	ENST00000503434.5	TSL:1	c.-4+1422T>C		intron	N/A	ENSP00000423021.1	O95436-2
	SLC34A2	ENST00000504570.5	TSL:1	c.-4+2096T>C		intron	N/A	ENSP00000425501.1	O95436-2

Frequencies

GnomAD3 genomes AF: 0.265 AC: 40323 AN: 151986 Hom.: 6580 Cov.: 32

Gnomad AFR AF: 0.0660

Gnomad AMI AF: 0.322

Gnomad AMR AF: 0.351

Gnomad ASJ AF: 0.344

Gnomad EAS AF: 0.283

Gnomad SAS AF: 0.345

Gnomad FIN AF: 0.355

Gnomad MID AF: 0.339

Gnomad NFE AF: 0.340

Gnomad OTH AF: 0.297

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

GnomAD4 genome AF: 0.265 AC: 40330 AN: 152104 Hom.: 6586 Cov.: 32 AF XY: 0.268 AC XY: 19946 AN XY: 74360

African (AFR) AF: 0.0658 AC: 2734 AN: 41538

American (AMR) AF: 0.352 AC: 5377 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.344 AC: 1192 AN: 3470

East Asian (EAS) AF: 0.283 AC: 1463 AN: 5168

South Asian (SAS) AF: 0.343 AC: 1653 AN: 4814

European-Finnish (FIN) AF: 0.355 AC: 3752 AN: 10562

Middle Eastern (MID) AF: 0.347 AC: 102 AN: 294

European-Non Finnish (NFE) AF: 0.340 AC: 23130 AN: 67960

Other (OTH) AF: 0.301 AC: 635 AN: 2112

Alfa AF: 0.309 Hom.: 7867

Bravo AF: 0.257

Asia WGS AF: 0.310 AC: 1076 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	7.2
DANN	Benign	0.70
PhyloP100		1.0
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: rs12501856; hg19: chr4-25659608;