rs12727528

Variant names:

• chr1-205925474-G-A
• rs12727528
• NM_052934.4:c.1390-985C>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.1390-985C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0964 in 152,260 control chromosomes in the GnomAD database, including 905 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 0.096 (905 hom., cov: 32)
• Consequence: SLC26A9 NM_052934.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.26
• Publications: 4 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=-0.85).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.164 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC26A9	NM_052934.4	c.1390-985C>T		intron_variant	Intron 12 of 20	ENST00000367135.8	NP_443166.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC26A9	ENST00000367135.8	c.1390-985C>T		intron_variant	Intron 12 of 20	1	NM_052934.4	ENSP00000356103.3
SLC26A9	ENST00000340781.8	c.1390-985C>T		intron_variant	Intron 11 of 20	1		ENSP00000341682.4
SLC26A9	ENST00000367134.2	c.1390-985C>T		intron_variant	Intron 12 of 21	5		ENSP00000356102.2
SLC26A9	ENST00000491127.5	n.774-985C>T		intron_variant	Intron 4 of 12	2

Frequencies

GnomAD3 genomes AF: 0.0963 AC: 14648 AN: 152142 Hom.: 900 Cov.: 32

Gnomad AFR AF: 0.167

Gnomad AMI AF: 0.104

Gnomad AMR AF: 0.0717

Gnomad ASJ AF: 0.117

Gnomad EAS AF: 0.00115

Gnomad SAS AF: 0.0464

Gnomad FIN AF: 0.0427

Gnomad MID AF: 0.120

Gnomad NFE AF: 0.0759

Gnomad OTH AF: 0.113

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

GnomAD4 genome AF: 0.0964 AC: 14672 AN: 152260 Hom.: 905 Cov.: 32 AF XY: 0.0925 AC XY: 6887 AN XY: 74444

African (AFR) AF: 0.168 AC: 6960 AN: 41532

American (AMR) AF: 0.0715 AC: 1094 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.117 AC: 405 AN: 3470

East Asian (EAS) AF: 0.000964 AC: 5 AN: 5186

South Asian (SAS) AF: 0.0466 AC: 225 AN: 4828

European-Finnish (FIN) AF: 0.0427 AC: 453 AN: 10606

Middle Eastern (MID) AF: 0.122 AC: 36 AN: 294

European-Non Finnish (NFE) AF: 0.0759 AC: 5161 AN: 68020

Other (OTH) AF: 0.113 AC: 238 AN: 2112

Alfa AF: 0.0884 Hom.: 874

Bravo AF: 0.103

Asia WGS AF: 0.0290 AC: 101 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	0.55
DANN	Benign	0.45
PhyloP100		-1.3
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: rs12727528; hg19: chr1-205894602;