1-205921551-T-C

Variant names:

• chr1-205921551-T-C
• rs12759719
• NM_052934.4:c.2055+15A>G

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_052934.4(SLC26A9):​c.2055+15A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.906 in 1,599,470 control chromosomes in the GnomAD database, including 657,383 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.91 (63227 hom., cov: 32)
  • Exomes 𝑓: 0.91 (594156 hom.)
• Consequence: SLC26A9 NM_052934.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.916
• Publications: 7 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BP6: Variant 1-205921551-T-C is Benign according to our data. Variant chr1-205921551-T-C is described in ClinVar as Benign. ClinVar VariationId is 403454.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.919 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC26A9	NM_052934.4	c.2055+15A>G		intron_variant	Intron 17 of 20	ENST00000367135.8	NP_443166.1
SLC26A9	NM_134325.3	c.2055+15A>G		intron_variant	Intron 17 of 21		NP_599152.2
SLC26A9	XM_011509121.3	c.1788+15A>G		intron_variant	Intron 16 of 19		XP_011507423.1
SLC26A9	XM_011509122.3	c.1563+15A>G		intron_variant	Intron 14 of 17		XP_011507424.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC26A9	ENST00000367135.8	c.2055+15A>G		intron_variant	Intron 17 of 20	1	NM_052934.4	ENSP00000356103.3
SLC26A9	ENST00000340781.8	c.2055+15A>G		intron_variant	Intron 16 of 20	1		ENSP00000341682.4
SLC26A9	ENST00000367134.2	c.2055+15A>G		intron_variant	Intron 17 of 21	5		ENSP00000356102.2
SLC26A9	ENST00000491127.5	n.1439+15A>G		intron_variant	Intron 9 of 12	2

Frequencies

GnomAD3 genomes AF: 0.911 AC: 138639 AN: 152106 Hom.: 63176 Cov.: 32

Gnomad AFR AF: 0.923

Gnomad AMI AF: 0.950

Gnomad AMR AF: 0.929

Gnomad ASJ AF: 0.891

Gnomad EAS AF: 0.911

Gnomad SAS AF: 0.942

Gnomad FIN AF: 0.902

Gnomad MID AF: 0.883

Gnomad NFE AF: 0.901

Gnomad OTH AF: 0.910

GnomAD2 exomes AF: 0.916 AC: 214436 AN: 234226 AF XY: 0.915

Gnomad AFR exome AF: 0.922

Gnomad AMR exome AF: 0.950

Gnomad ASJ exome AF: 0.897

Gnomad EAS exome AF: 0.924

Gnomad FIN exome AF: 0.907

Gnomad NFE exome AF: 0.900

Gnomad OTH exome AF: 0.900

GnomAD4 exome AF: 0.906 AC: 1311046 AN: 1447246 Hom.: 594156 Cov.: 60 AF XY: 0.906 AC XY: 652035 AN XY: 719446

African (AFR) AF: 0.925 AC: 30860 AN: 33362

American (AMR) AF: 0.946 AC: 41895 AN: 44294

Ashkenazi Jewish (ASJ) AF: 0.901 AC: 23449 AN: 26036

East Asian (EAS) AF: 0.906 AC: 35717 AN: 39424

South Asian (SAS) AF: 0.938 AC: 80063 AN: 85348

European-Finnish (FIN) AF: 0.910 AC: 40088 AN: 44070

Middle Eastern (MID) AF: 0.911 AC: 5209 AN: 5716

European-Non Finnish (NFE) AF: 0.901 AC: 999635 AN: 1108872

Other (OTH) AF: 0.900 AC: 54130 AN: 60124

GnomAD4 genome AF: 0.911 AC: 138747 AN: 152224 Hom.: 63227 Cov.: 32 AF XY: 0.913 AC XY: 67952 AN XY: 74432

African (AFR) AF: 0.923 AC: 38328 AN: 41538

American (AMR) AF: 0.929 AC: 14221 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.891 AC: 3095 AN: 3472

East Asian (EAS) AF: 0.911 AC: 4703 AN: 5164

South Asian (SAS) AF: 0.941 AC: 4538 AN: 4820

European-Finnish (FIN) AF: 0.902 AC: 9571 AN: 10614

Middle Eastern (MID) AF: 0.874 AC: 257 AN: 294

European-Non Finnish (NFE) AF: 0.901 AC: 61241 AN: 67990

Other (OTH) AF: 0.912 AC: 1927 AN: 2114

Alfa AF: 0.898 Hom.: 12390

Bravo AF: 0.914

Asia WGS AF: 0.914 AC: 3178 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

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	-0.93
CADD	Benign	0.64
DANN	Benign	0.28
PhyloP100		-0.92
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: rs12759719; hg19: chr1-205890679;