NM_000112.4:c.-478G>C

Variant names:

• chr5-149960527-G-C
• rs1541915
• NM_000112.4:c.-478G>C

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_000112.4(SLC26A2):​c.-478G>C variant causes a upstream gene change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000263 in 152,310 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 0.000026 (0 hom., cov: 36)
• Consequence: SLC26A2 NM_000112.4 upstream_gene
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.96

Genes affected

SLC26A2 (HGNC:10994): (solute carrier family 26 member 2) The diastrophic dysplasia sulfate transporter is a transmembrane glycoprotein implicated in the pathogenesis of several human chondrodysplasias. It apparently is critical in cartilage for sulfation of proteoglycans and matrix organization. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.72).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC26A2	NM_000112.4	c.-478G>C		upstream_gene_variant		ENST00000286298.5	NP_000103.2
SLC26A2	XM_017009191.3	c.-478G>C		upstream_gene_variant			XP_016864680.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC26A2	ENST00000286298.5	c.-478G>C		upstream_gene_variant		1	NM_000112.4	ENSP00000286298.4
SLC26A2	ENST00000690410.1	n.-246G>C		upstream_gene_variant

Frequencies

GnomAD3 genomes AF: 0.0000329 AC: 5 AN: 152192 Hom.: 0 Cov.: 36

Gnomad AFR AF: 0.0000241

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00949

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

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

GnomAD4 genome AF: 0.0000263 AC: 4 AN: 152310 Hom.: 0 Cov.: 36 AF XY: 0.0000134 AC XY: 1 AN XY: 74468

Gnomad4 AFR AF: 0.0000240

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000207

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00

Gnomad4 OTH AF: 0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.72
CADD	Benign	0.021
DANN	Benign	0.42

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs1541915; hg19: chr5-149340090;