7-107660945-T-G

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_000441.2(SLC26A4):c.-4+90T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0447 in 152,242 control chromosomes in the GnomAD database, including 175 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.045 (175 hom., cov: 32)
  • Exomes 𝑓: 0.048 (0 hom.)
• Consequence: SLC26A4 NM_000441.2 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.35

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 Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BP6: Variant 7-107660945-T-G is Benign according to our data. Variant chr7-107660945-T-G is described in ClinVar as [Benign]. Clinvar id is 1267269.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0506 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLC26A4	NM_000441.2	c.-4+90T>G		intron_variant		ENST00000644269.2
SLC26A4-AS1	NR_028137.1	n.197+657A>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC26A4	ENST00000644269.2	c.-4+90T>G		intron_variant			NM_000441.2	P1
SLC26A4-AS1	ENST00000668981.1	n.257+657A>C		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.0447 AC: 6795 AN: 151958 Hom.: 175 Cov.: 32

Gnomad AFR AF: 0.0498

Gnomad AMI AF: 0.0614

Gnomad AMR AF: 0.0294

Gnomad ASJ AF: 0.0323

Gnomad EAS AF: 0.00136

Gnomad SAS AF: 0.0241

Gnomad FIN AF: 0.0328

Gnomad MID AF: 0.0696

Gnomad NFE AF: 0.0520

Gnomad OTH AF: 0.0417

GnomAD4 exome AF: 0.0476 AC: 8 AN: 168 Hom.: 0 Cov.: 0 AF XY: 0.0614 AC XY: 7 AN XY: 114

Gnomad4 AFR exome AF: 0.250

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.250

Gnomad4 NFE exome AF: 0.0352

Gnomad4 OTH exome AF: 0.250

GnomAD4 genome AF: 0.0447 AC: 6802 AN: 152074 Hom.: 175 Cov.: 32 AF XY: 0.0430 AC XY: 3194 AN XY: 74334

Gnomad4 AFR AF: 0.0500

Gnomad4 AMR AF: 0.0293

Gnomad4 ASJ AF: 0.0323

Gnomad4 EAS AF: 0.00136

Gnomad4 SAS AF: 0.0242

Gnomad4 FIN AF: 0.0328

Gnomad4 NFE AF: 0.0520

Gnomad4 OTH AF: 0.0413

Alfa AF: 0.0494 Hom.: 23

Bravo AF: 0.0440

Asia WGS AF: 0.0200 AC: 69 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Dec 10, 2018

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
Cadd	Benign	0.76
Dann	Benign	0.43

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: rs73191607; hg19: chr7-107301390;