chr1-205914934-T-C

Variant names:

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The ENST00000340781.8(SLC26A9):c.2622A>G(p.Pro874Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0841 in 1,614,076 control chromosomes in the GnomAD database, including 6,264 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.10 ( 894 hom., cov: 32)

Exomes 𝑓: 0.082 ( 5370 hom. )

Consequence

SLC26A9
ENST00000340781.8 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.0320

Publications

7 publications found

Variant links:

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

SLC26A9 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.9).

BP6

Variant 1-205914934-T-C is Benign according to our data. Variant chr1-205914934-T-C is described in ClinVar as Benign. ClinVar VariationId is 403450.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=0.032 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.157 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC26A9	NM_052934.4 link	c.*423A>G		3_prime_UTR_variant	Exon 21 of 21	ENST00000367135.8	NP_443166.1	Q7LBE3-1
SLC26A9	NM_134325.3 link	c.2622A>G	p.Pro874Pro	synonymous_variant	Exon 22 of 22		NP_599152.2	Q7LBE3-2B3KXK1
SLC26A9	XM_011509121.3 link	c.*423A>G		3_prime_UTR_variant	Exon 20 of 20		XP_011507423.1
SLC26A9	XM_011509122.3 link	c.*423A>G		3_prime_UTR_variant	Exon 18 of 18		XP_011507424.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
SLC26A9	ENST00000340781.8 link	c.2622A>G	p.Pro874Pro	synonymous_variant	Exon 21 of 21	1		ENSP00000341682.4	Q7LBE3-2
SLC26A9	ENST00000367135.8 link	c.*423A>G		3_prime_UTR_variant	Exon 21 of 21	1	NM_052934.4	ENSP00000356103.3	Q7LBE3-1
SLC26A9	ENST00000367134.2 link	c.2622A>G	p.Pro874Pro	synonymous_variant	Exon 22 of 22	5		ENSP00000356102.2	Q7LBE3-2
SLC26A9	ENST00000491127.5 link	n.2183A>G		non_coding_transcript_exon_variant	Exon 13 of 13	2

Frequencies

GnomAD3 genomes

AF:

0.101

AC:

15336

AN:

152138

Hom.:

890

Cov.:

show subpopulations

Gnomad AFR

AF:

0.160

Gnomad AMI

AF:

0.130

Gnomad AMR

AF:

0.0753

Gnomad ASJ

AF:

0.114

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.0259

Gnomad FIN

AF:

0.0623

Gnomad MID

AF:

0.0918

Gnomad NFE

AF:

0.0886

Gnomad OTH

AF:

0.102

GnomAD2 exomes

AF:

0.0742

AC:

18631

AN:

251188

AF XY:

0.0724

show subpopulations

Gnomad AFR exome

AF:

0.163

Gnomad AMR exome

AF:

0.0523

Gnomad ASJ exome

AF:

0.108

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0623

Gnomad NFE exome

AF:

0.0902

Gnomad OTH exome

AF:

0.0860

GnomAD4 exome

AF:

0.0824

AC:

120443

AN:

1461820

Hom.:

5370

Cov.:

AF XY:

0.0811

AC XY:

58985

AN XY:

727220

show subpopulations

African (AFR)

AF:

0.168

AC:

5618

AN:

33480

American (AMR)

AF:

0.0543

AC:

2426

AN:

44710

Ashkenazi Jewish (ASJ)

AF:

0.108

AC:

2825

AN:

26128

East Asian (EAS)

AF:

0.000101

AC:

AN:

39700

South Asian (SAS)

AF:

0.0307

AC:

2652

AN:

86248

European-Finnish (FIN)

AF:

0.0640

AC:

3418

AN:

53420

Middle Eastern (MID)

AF:

0.116

AC:

671

AN:

5766

European-Non Finnish (NFE)

AF:

0.0882

AC:

98062

AN:

1111974

Other (OTH)

AF:

0.0789

AC:

4767

AN:

60394

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.479

Heterozygous variant carriers

6809

13617

20426

27234

34043

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

3546

7092

10638

14184

17730

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.101

AC:

15353

AN:

152256

Hom.:

894

Cov.:

AF XY:

0.0965

AC XY:

7182

AN XY:

74438

show subpopulations

African (AFR)

AF:

0.160

AC:

6632

AN:

41500

American (AMR)

AF:

0.0752

AC:

1151

AN:

15304

Ashkenazi Jewish (ASJ)

AF:

0.114

AC:

397

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5186

South Asian (SAS)

AF:

0.0259

AC:

125

AN:

4822

European-Finnish (FIN)

AF:

0.0623

AC:

662

AN:

10618

Middle Eastern (MID)

AF:

0.0952

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0886

AC:

6025

AN:

68034

Other (OTH)

AF:

0.101

AC:

214

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

722

1444

2165

2887

3609

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

170

340

510

680

850

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0958

Hom.:

1108

Bravo

AF:

0.106

EpiCase

AF:

0.0965

EpiControl

AF:

0.0978

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:1

Mar 29, 2016

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: Frequency -

not provided

Benign:1

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.90

CADD

Benign

3.8

(source)

DANN

Benign

0.42

PhyloP100

0.032

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over