rs11240594

Variant names:

• chr1-205927107-G-A
• rs11240594
• NM_052934.4:c.1293+104C>T

Variant summary

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

The NM_052934.4(SLC26A9):​c.1293+104C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.191 in 1,182,134 control chromosomes in the GnomAD database, including 25,944 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 0.20 (3460 hom., cov: 32)
  • Exomes 𝑓: 0.19 (22484 hom.)
• Consequence: SLC26A9 NM_052934.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.311
• Publications: 19 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=-0.86).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.552 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC26A9	NM_052934.4	c.1293+104C>T		intron_variant	Intron 11 of 20	ENST00000367135.8	NP_443166.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC26A9	ENST00000367135.8	c.1293+104C>T		intron_variant	Intron 11 of 20	1	NM_052934.4	ENSP00000356103.3
SLC26A9	ENST00000340781.8	c.1293+104C>T		intron_variant	Intron 10 of 20	1		ENSP00000341682.4
SLC26A9	ENST00000367134.2	c.1293+104C>T		intron_variant	Intron 11 of 21	5		ENSP00000356102.2
SLC26A9	ENST00000491127.5	n.677+104C>T		intron_variant	Intron 3 of 12	2

Frequencies

GnomAD3 genomes AF: 0.197 AC: 29952 AN: 152064 Hom.: 3456 Cov.: 32

Gnomad AFR AF: 0.225

Gnomad AMI AF: 0.239

Gnomad AMR AF: 0.195

Gnomad ASJ AF: 0.215

Gnomad EAS AF: 0.569

Gnomad SAS AF: 0.270

Gnomad FIN AF: 0.118

Gnomad MID AF: 0.184

Gnomad NFE AF: 0.157

Gnomad OTH AF: 0.215

GnomAD4 exome AF: 0.190 AC: 196055 AN: 1029952 Hom.: 22484 AF XY: 0.193 AC XY: 101502 AN XY: 527264

African (AFR) AF: 0.222 AC: 5498 AN: 24798

American (AMR) AF: 0.240 AC: 10044 AN: 41852

Ashkenazi Jewish (ASJ) AF: 0.208 AC: 4633 AN: 22230

East Asian (EAS) AF: 0.575 AC: 21503 AN: 37404

South Asian (SAS) AF: 0.272 AC: 20063 AN: 73726

European-Finnish (FIN) AF: 0.134 AC: 6837 AN: 51004

Middle Eastern (MID) AF: 0.265 AC: 1116 AN: 4210

European-Non Finnish (NFE) AF: 0.160 AC: 116786 AN: 728722

Other (OTH) AF: 0.208 AC: 9575 AN: 46006

GnomAD4 genome AF: 0.197 AC: 29992 AN: 152182 Hom.: 3460 Cov.: 32 AF XY: 0.199 AC XY: 14770 AN XY: 74388

African (AFR) AF: 0.225 AC: 9340 AN: 41518

American (AMR) AF: 0.196 AC: 2991 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.215 AC: 745 AN: 3472

East Asian (EAS) AF: 0.569 AC: 2936 AN: 5162

South Asian (SAS) AF: 0.271 AC: 1307 AN: 4822

European-Finnish (FIN) AF: 0.118 AC: 1250 AN: 10594

Middle Eastern (MID) AF: 0.194 AC: 57 AN: 294

European-Non Finnish (NFE) AF: 0.157 AC: 10699 AN: 68000

Other (OTH) AF: 0.213 AC: 449 AN: 2110

Alfa AF: 0.183 Hom.: 12969

Bravo AF: 0.208

Asia WGS AF: 0.380 AC: 1321 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.53
DANN	Benign	0.78
PhyloP100		-0.31
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: rs11240594; hg19: chr1-205896235;