1-205930467-T-C

Variant names:

• chr1-205930467-T-C
• rs7512462
• NM_052934.4:c.553-411A>G

Variant summary

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

The NM_052934.4(SLC26A9):​c.553-411A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.378 in 152,024 control chromosomes in the GnomAD database, including 11,545 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 0.38 (11545 hom., cov: 32)
• Consequence: SLC26A9 NM_052934.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0160
• Publications: 25 publications found

Genes affected

SLC26A9 (HGNC:14469): (solute carrier family 26 member 9) This gene is one member of a family of sulfate/anion transporter genes. Family members are well conserved in their genomic (number and size of exons) and protein (aa length among species) structures yet have markedly different tissue expression patterns. The product of this gene is a highly selective chloride ion channel regulated by WNK kinases. Alternative splicing results in multiple transcript variants encoding differing isoforms.[provided by RefSeq, Dec 2008]

SLC26A9 Gene-Disease associations (from GenCC):

• cystic fibrosis

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.49 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_052934.4. 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
	SLC26A9	NM_052934.4	MANE Select	c.553-411A>G		intron	N/A	NP_443166.1
	SLC26A9	NM_134325.3		c.553-411A>G		intron	N/A	NP_599152.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC26A9	ENST00000367135.8	TSL:1 MANE Select	c.553-411A>G		intron	N/A	ENSP00000356103.3
	SLC26A9	ENST00000340781.8	TSL:1	c.553-411A>G		intron	N/A	ENSP00000341682.4
	SLC26A9	ENST00000367134.2	TSL:5	c.553-411A>G		intron	N/A	ENSP00000356102.2

Frequencies

GnomAD3 genomes AF: 0.378 AC: 57385 AN: 151906 Hom.: 11543 Cov.: 32

Gnomad AFR AF: 0.262

Gnomad AMI AF: 0.453

Gnomad AMR AF: 0.499

Gnomad ASJ AF: 0.398

Gnomad EAS AF: 0.273

Gnomad SAS AF: 0.507

Gnomad FIN AF: 0.449

Gnomad MID AF: 0.506

Gnomad NFE AF: 0.405

Gnomad OTH AF: 0.405

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

GnomAD4 genome AF: 0.378 AC: 57401 AN: 152024 Hom.: 11545 Cov.: 32 AF XY: 0.386 AC XY: 28642 AN XY: 74292

African (AFR) AF: 0.262 AC: 10855 AN: 41484

American (AMR) AF: 0.499 AC: 7626 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.398 AC: 1382 AN: 3472

East Asian (EAS) AF: 0.273 AC: 1413 AN: 5174

South Asian (SAS) AF: 0.506 AC: 2436 AN: 4814

European-Finnish (FIN) AF: 0.449 AC: 4738 AN: 10558

Middle Eastern (MID) AF: 0.486 AC: 142 AN: 292

European-Non Finnish (NFE) AF: 0.405 AC: 27526 AN: 67932

Other (OTH) AF: 0.412 AC: 870 AN: 2110

Alfa AF: 0.395 Hom.: 12968

Bravo AF: 0.373

Asia WGS AF: 0.389 AC: 1348 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	2.8
DANN	Benign	0.66
PhyloP100		-0.016
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: rs7512462; hg19: chr1-205899595;