rs16856470

Variant names:

• chr1-205920201-C-T
• rs16856470
• NM_052934.4:c.2085G>A

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_052934.4(SLC26A9):​c.2085G>A​(p.Val695Val) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0703 in 1,613,834 control chromosomes in the GnomAD database, including 4,294 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.070 (385 hom., cov: 32)
  • Exomes 𝑓: 0.070 (3909 hom.)
• Consequence: SLC26A9 NM_052934.4 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 1.01
• Publications: 11 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 -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.5).
• BP6: Variant 1-205920201-C-T is Benign according to our data. Variant chr1-205920201-C-T is described in ClinVar as Benign. ClinVar VariationId is 403453.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=1.01 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0755 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC26A9	NM_052934.4	MANE Select	c.2085G>A	p.Val695Val	synonymous	Exon 18 of 21	NP_443166.1
	SLC26A9	NM_134325.3		c.2085G>A	p.Val695Val	synonymous	Exon 18 of 22	NP_599152.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC26A9	ENST00000367135.8	TSL:1 MANE Select	c.2085G>A	p.Val695Val	synonymous	Exon 18 of 21	ENSP00000356103.3
	SLC26A9	ENST00000340781.8	TSL:1	c.2085G>A	p.Val695Val	synonymous	Exon 17 of 21	ENSP00000341682.4
	SLC26A9	ENST00000367134.2	TSL:5	c.2085G>A	p.Val695Val	synonymous	Exon 18 of 22	ENSP00000356102.2

Frequencies

GnomAD3 genomes AF: 0.0700 AC: 10653 AN: 152126 Hom.: 384 Cov.: 32

Gnomad AFR AF: 0.0735

Gnomad AMI AF: 0.104

Gnomad AMR AF: 0.0631

Gnomad ASJ AF: 0.133

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.0317

Gnomad FIN AF: 0.0425

Gnomad MID AF: 0.114

Gnomad NFE AF: 0.0772

Gnomad OTH AF: 0.0936

GnomAD2 exomes AF: 0.0626 AC: 15744 AN: 251478 AF XY: 0.0627

Gnomad AFR exome AF: 0.0773

Gnomad AMR exome AF: 0.0446

Gnomad ASJ exome AF: 0.130

Gnomad EAS exome AF: 0.0000544

Gnomad FIN exome AF: 0.0462

Gnomad NFE exome AF: 0.0803

Gnomad OTH exome AF: 0.0813

GnomAD4 exome AF: 0.0703 AC: 102798 AN: 1461590 Hom.: 3909 Cov.: 31 AF XY: 0.0700 AC XY: 50889 AN XY: 727120

African (AFR) AF: 0.0713 AC: 2385 AN: 33472

American (AMR) AF: 0.0465 AC: 2078 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.130 AC: 3392 AN: 26114

East Asian (EAS) AF: 0.000151 AC: 6 AN: 39694

South Asian (SAS) AF: 0.0322 AC: 2779 AN: 86246

European-Finnish (FIN) AF: 0.0473 AC: 2529 AN: 53416

Middle Eastern (MID) AF: 0.136 AC: 786 AN: 5762

European-Non Finnish (NFE) AF: 0.0759 AC: 84361 AN: 1111772

Other (OTH) AF: 0.0742 AC: 4482 AN: 60392

GnomAD4 genome AF: 0.0700 AC: 10655 AN: 152244 Hom.: 385 Cov.: 32 AF XY: 0.0670 AC XY: 4987 AN XY: 74442

African (AFR) AF: 0.0734 AC: 3047 AN: 41526

American (AMR) AF: 0.0629 AC: 962 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.133 AC: 462 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5182

South Asian (SAS) AF: 0.0317 AC: 153 AN: 4824

European-Finnish (FIN) AF: 0.0425 AC: 451 AN: 10606

Middle Eastern (MID) AF: 0.116 AC: 34 AN: 294

European-Non Finnish (NFE) AF: 0.0773 AC: 5255 AN: 68020

Other (OTH) AF: 0.0931 AC: 196 AN: 2106

Alfa AF: 0.0803 Hom.: 1045

Bravo AF: 0.0733

Asia WGS AF: 0.0160 AC: 54 AN: 3478

EpiCase AF: 0.0881

EpiControl AF: 0.0901

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.50
CADD	Benign	11
DANN	Benign	0.74
PhyloP100		1.0
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.13		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: rs16856470; hg19: chr1-205889329; COSMIC: COSV61605873; COSMIC: COSV61605873;