rs2240996

Variant names:

• chr4-25673478-C-A
• rs2240996
• NM_006424.3:c.1216+224C>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 1 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: Orphanet, Ambry Genetics, Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
SLC34A2	NM_006424.3	c.1216+224C>A		intron_variant	Intron 10 of 12	ENST00000382051.8	NP_006415.3
SLC34A2	NM_001177998.2	c.1213+224C>A		intron_variant	Intron 10 of 12		NP_001171469.2
SLC34A2	NM_001177999.2	c.1213+224C>A		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+224C>A		intron_variant	Intron 10 of 12	1	NM_006424.3	ENSP00000371483.3
SLC34A2	ENST00000503434.5	c.1213+224C>A		intron_variant	Intron 10 of 12	1		ENSP00000423021.1
SLC34A2	ENST00000504570.5	c.1213+224C>A		intron_variant	Intron 10 of 12	1		ENSP00000425501.1
SLC34A2	ENST00000645788.1	c.1213+224C>A		intron_variant	Intron 10 of 12			ENSP00000494094.1

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

African (AFR) AF: 0.435 AC: 18035 AN: 41430

American (AMR) AF: 0.209 AC: 3185 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.117 AC: 406 AN: 3468

East Asian (EAS) AF: 0.251 AC: 1299 AN: 5168

South Asian (SAS) AF: 0.0870 AC: 419 AN: 4818

European-Finnish (FIN) AF: 0.0955 AC: 1012 AN: 10594

Middle Eastern (MID) AF: 0.116 AC: 34 AN: 294

European-Non Finnish (NFE) AF: 0.113 AC: 7685 AN: 67976

Other (OTH) AF: 0.193 AC: 409 AN: 2116

Alfa AF: 0.167 Hom.: 5287

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
PhyloP100		-0.55
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2240996; hg19: chr4-25675100;