1-205921551-T-C

Position:

• chr1-205921551-T-C

Variant summary

Our verdict is Benign. Variant got -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

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]

ACMG classification

Verdict is Benign. Variant got -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 id 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/exons	MANE	Protein	UniProt
SLC26A9	NM_052934.4	c.2055+15A>G		intron_variant		ENST00000367135.8	NP_443166.1
SLC26A9	NM_134325.3	c.2055+15A>G		intron_variant			NP_599152.2
SLC26A9	XM_011509121.3	c.1788+15A>G		intron_variant			XP_011507423.1
SLC26A9	XM_011509122.3	c.1563+15A>G		intron_variant			XP_011507424.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLC26A9	ENST00000367135.8	c.2055+15A>G		intron_variant		1	NM_052934.4	ENSP00000356103	P1
SLC26A9	ENST00000340781.8	c.2055+15A>G		intron_variant		1		ENSP00000341682
SLC26A9	ENST00000367134.2	c.2055+15A>G		intron_variant		5		ENSP00000356102
SLC26A9	ENST00000491127.5	n.1439+15A>G		intron_variant, non_coding_transcript_variant		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

GnomAD3 exomes AF: 0.916 AC: 214436 AN: 234226 Hom.: 98202 AF XY: 0.915 AC XY: 116340 AN XY: 127166

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 SAS exome AF: 0.936

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

Gnomad4 AFR exome AF: 0.925

Gnomad4 AMR exome AF: 0.946

Gnomad4 ASJ exome AF: 0.901

Gnomad4 EAS exome AF: 0.906

Gnomad4 SAS exome AF: 0.938

Gnomad4 FIN exome AF: 0.910

Gnomad4 NFE exome AF: 0.901

Gnomad4 OTH exome AF: 0.900

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

Gnomad4 AFR AF: 0.923

Gnomad4 AMR AF: 0.929

Gnomad4 ASJ AF: 0.891

Gnomad4 EAS AF: 0.911

Gnomad4 SAS AF: 0.941

Gnomad4 FIN AF: 0.902

Gnomad4 NFE AF: 0.901

Gnomad4 OTH AF: 0.912

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

Benign, criteria provided, single submitter

clinical testing

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Mar 29, 2016

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

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

-

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.64
DANN	Benign	0.28

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

LitVar

Other links and lift over

dbSNP: rs12759719; hg19: chr1-205890679;