rs140918297
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Variant summary
Our verdict is Benign. Variant got -9 ACMG points: 2P and 11B. PM2BP4_ModerateBP6_Very_StrongBP7
The NM_000441.2(SLC26A4):c.1470C>T(p.Ile490=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000757 in 1,611,166 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Genomes: 𝑓 0.000066 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000077 ( 0 hom. )
Consequence
SLC26A4
NM_000441.2 synonymous
NM_000441.2 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 1.20
Genes affected
SLC26A4 (HGNC:8818): (solute carrier family 26 member 4) Mutations in this gene are associated with Pendred syndrome, the most common form of syndromic deafness, an autosomal-recessive disease. It is highly homologous to the SLC26A3 gene; they have similar genomic structures and this gene is located 3' of the SLC26A3 gene. The encoded protein has homology to sulfate transporters. [provided by RefSeq, Jul 2008]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -9 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.29).
BP6
?
Variant 7-107695965-C-T is Benign according to our data. Variant chr7-107695965-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 165253.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
?
Synonymous conserved (PhyloP=1.2 with no splicing effect.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SLC26A4 | NM_000441.2 | c.1470C>T | p.Ile490= | synonymous_variant | 13/21 | ENST00000644269.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SLC26A4 | ENST00000644269.2 | c.1470C>T | p.Ile490= | synonymous_variant | 13/21 | NM_000441.2 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000658 AC: 10AN: 152040Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.000394 AC: 99AN: 251414Hom.: 0 AF XY: 0.000265 AC XY: 36AN XY: 135878
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GnomAD4 exome AF: 0.0000768 AC: 112AN: 1459008Hom.: 0 Cov.: 29 AF XY: 0.0000592 AC XY: 43AN XY: 726020
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GnomAD4 genome ? AF: 0.0000657 AC: 10AN: 152158Hom.: 0 Cov.: 32 AF XY: 0.0000807 AC XY: 6AN XY: 74366
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ClinVar
Significance: Benign/Likely benign
Submissions summary: Benign:3
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not provided Benign:2
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 29, 2024 | - - |
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | May 12, 2021 | - - |
not specified Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | Aug 02, 2018 | The p.Ile490Ile variant in SLC26A4 is classified as likely benign since it is no t expected to have clinical significance because it does not alter an amino acid residue, it is not located within the splice consensus sequence, and it has bee n identified in 0.29% (101/34404) of Latino chromosomes by the Genome Aggregatio n Database (gnomAD, http://gnomad.broadinstitute.org). - |
Computational scores
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at