7-107661444-C-T

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_Strong BP6_Moderate

The NM_000441.2(SLC26A4):c.-3-195C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00501 in 646,704 control chromosomes in the GnomAD database, including 16 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0043 (1 hom., cov: 32)
  • Exomes 𝑓: 0.0052 (15 hom.)
• Consequence: SLC26A4 NM_000441.2 intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.250

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]

SLC26A4-AS1 (HGNC:22385): (SLC26A4 antisense RNA 1)

ACMG classification

Verdict is Likely_benign. Variant got -6 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.69).
• BP6: Variant 7-107661444-C-T is Benign according to our data. Variant chr7-107661444-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 1198155.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLC26A4	NM_000441.2	c.-3-195C>T		intron_variant		ENST00000644269.2
SLC26A4-AS1	NR_028137.1	n.197+158G>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC26A4	ENST00000644269.2	c.-3-195C>T		intron_variant			NM_000441.2	P1
SLC26A4-AS1	ENST00000668981.1	n.257+158G>A		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.00426 AC: 648 AN: 152238 Hom.: 1 Cov.: 32

Gnomad AFR AF: 0.000531

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00118

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00269

Gnomad FIN AF: 0.0238

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00497

Gnomad OTH AF: 0.00191

GnomAD4 exome AF: 0.00525 AC: 2594 AN: 494348 Hom.: 15 Cov.: 5 AF XY: 0.00503 AC XY: 1308 AN XY: 259964

Gnomad4 AFR exome AF: 0.000503

Gnomad4 AMR exome AF: 0.00107

Gnomad4 ASJ exome AF: 0.000733

Gnomad4 EAS exome AF: 0.0000319

Gnomad4 SAS exome AF: 0.00425

Gnomad4 FIN exome AF: 0.0248

Gnomad4 NFE exome AF: 0.00495

Gnomad4 OTH exome AF: 0.00373

GnomAD4 genome AF: 0.00425 AC: 648 AN: 152356 Hom.: 1 Cov.: 32 AF XY: 0.00486 AC XY: 362 AN XY: 74506

Gnomad4 AFR AF: 0.000529

Gnomad4 AMR AF: 0.00118

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00269

Gnomad4 FIN AF: 0.0238

Gnomad4 NFE AF: 0.00497

Gnomad4 OTH AF: 0.00189

Alfa AF: 0.00138 Hom.: 1

Bravo AF: 0.00261

Asia WGS AF: 0.000577 AC: 2 AN: 3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

Dec 22, 2018

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.69
Cadd	Benign	6.1
Dann	Benign	0.75

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.080		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: rs55706020; hg19: chr7-107301889;