5-149960527-G-T

Variant names:

• chr5-149960527-G-T
• rs1541915
• ENST00000775979.1:n.51C>A

Variant summary

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

The ENST00000775979.1(ENSG00000301078):​n.51C>A variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.581 in 152,264 control chromosomes in the GnomAD database, including 26,283 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 0.58 (26283 hom., cov: 36)
• Consequence: ENSG00000301078 ENST00000775979.1 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.96
• Publications: 9 publications found

Genes affected

ENSG00000301078 (HGNC:):

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]

SLC26A2 Gene-Disease associations (from GenCC):

• achondrogenesis type IB

  Inheritance: AR Classification: DEFINITIVE, MODERATE, SUPPORTIVE Submitted by: Orphanet, ClinGen, G2P, Ambry Genetics
• atelosteogenesis type II

  Inheritance: AR Classification: DEFINITIVE, MODERATE, SUPPORTIVE Submitted by: ClinGen, Ambry Genetics, Orphanet
• diastrophic dysplasia

  Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Orphanet, Ambry Genetics, Labcorp Genetics (formerly Invitae), ClinGen
• multiple epiphyseal dysplasia

  Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen
• multiple epiphyseal dysplasia type 4

  Inheritance: AR Classification: DEFINITIVE, MODERATE, SUPPORTIVE Submitted by: Orphanet, G2P, Ambry Genetics
• SLC26A2-related skeletal dysplasia

  Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen
• skeletal dysplasia

  Inheritance: AR Classification: STRONG Submitted by: PanelApp Australia

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.72).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.681 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000775979.1. 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
	SLC26A2	NM_000112.4	MANE Select	c.-478G>T		upstream_gene	N/A	NP_000103.2	P50443

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ENSG00000301078	ENST00000775979.1		n.51C>A		non_coding_transcript_exon	Exon 1 of 1
	SLC26A2	ENST00000286298.5	TSL:1 MANE Select	c.-478G>T		upstream_gene	N/A	ENSP00000286298.4	P50443
	SLC26A2	ENST00000690410.1		n.-246G>T		upstream_gene	N/A

Frequencies

GnomAD3 genomes AF: 0.580 AC: 88305 AN: 152146 Hom.: 26250 Cov.: 36

Gnomad AFR AF: 0.687

Gnomad AMI AF: 0.481

Gnomad AMR AF: 0.452

Gnomad ASJ AF: 0.543

Gnomad EAS AF: 0.516

Gnomad SAS AF: 0.487

Gnomad FIN AF: 0.616

Gnomad MID AF: 0.430

Gnomad NFE AF: 0.555

Gnomad OTH AF: 0.527

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

GnomAD4 genome AF: 0.581 AC: 88393 AN: 152264 Hom.: 26283 Cov.: 36 AF XY: 0.579 AC XY: 43067 AN XY: 74444

African (AFR) AF: 0.688 AC: 28576 AN: 41558

American (AMR) AF: 0.452 AC: 6925 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.543 AC: 1886 AN: 3472

East Asian (EAS) AF: 0.516 AC: 2670 AN: 5172

South Asian (SAS) AF: 0.489 AC: 2359 AN: 4826

European-Finnish (FIN) AF: 0.616 AC: 6529 AN: 10604

Middle Eastern (MID) AF: 0.415 AC: 122 AN: 294

European-Non Finnish (NFE) AF: 0.555 AC: 37774 AN: 68006

Other (OTH) AF: 0.526 AC: 1113 AN: 2116

Alfa AF: 0.541 Hom.: 8850

Bravo AF: 0.572

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.72
CADD	Benign	0.019
DANN	Benign	0.52
PhyloP100		-2.0
PromoterAI		-0.16	Neutral

Splicing

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs1541915;

hg19: chr5-149340090;