rs17154282

Variant names:

• chr7-107660793-C-G
• rs17154282
• ENST00000888701.1:c.-849C>G

Your query was ambiguous. Multiple possible variants found:

• chr7-107660793-C-G
• chr7-107660793-C-T

Variant summary

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

The ENST00000888701.1(SLC26A4):​c.-849C>G variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0768 in 152,214 control chromosomes in the GnomAD database, including 1,495 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★). The gene SLC26A4 is included in the ClinGen Criteria Specification Registry.

• Frequency:
  • Genomes: 𝑓 0.077 (1495 hom., cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: SLC26A4 ENST00000888701.1 5_prime_UTR
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: -0.122
• Publications: 7 publications found

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

Specifications for SLC26A4 are available in the ClinGen Criteria Specification Registry and recommended for reference when assigning criteria.

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.62).
• BP6: Variant 7-107660793-C-G is Benign according to our data. Variant chr7-107660793-C-G is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 43487.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.259 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000888701.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC26A4-AS1	NR_028137.1		n.198-587G>C		intron	N/A
	SLC26A4	NM_000441.2	MANE Select	c.-66C>G		upstream_gene	N/A	NP_000432.1	O43511-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC26A4	ENST00000888701.1		c.-849C>G		5_prime_UTR	Exon 1 of 20	ENSP00000558760.1
	SLC26A4-AS1	ENST00000658036.1		n.1104G>C		non_coding_transcript_exon	Exon 2 of 2
	SLC26A4-AS1	ENST00000689362.1		n.1040G>C		non_coding_transcript_exon	Exon 1 of 1

Frequencies

GnomAD3 genomes AF: 0.0767 AC: 11663 AN: 152096 Hom.: 1495 Cov.: 32

Gnomad AFR AF: 0.263

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0330

Gnomad ASJ AF: 0.00692

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.000414

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0316

Gnomad NFE AF: 0.00131

Gnomad OTH AF: 0.0721

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 38 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 32

African (AFR) AF: 0.00 AC: 0 AN: 2

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 34

Other (OTH) AF: 0.00 AC: 0 AN: 2

GnomAD4 genome AF: 0.0768 AC: 11686 AN: 152214 Hom.: 1495 Cov.: 32 AF XY: 0.0727 AC XY: 5410 AN XY: 74436

African (AFR) AF: 0.263 AC: 10907 AN: 41500

American (AMR) AF: 0.0328 AC: 502 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.00692 AC: 24 AN: 3468

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5178

South Asian (SAS) AF: 0.000415 AC: 2 AN: 4824

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10614

Middle Eastern (MID) AF: 0.0340 AC: 10 AN: 294

European-Non Finnish (NFE) AF: 0.00131 AC: 89 AN: 68018

Other (OTH) AF: 0.0714 AC: 151 AN: 2116

Alfa AF: 0.0147 Hom.: 22

Bravo AF: 0.0875

ClinVar

ClinVar submissions

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	Pendred syndrome (2)
-	-	1	Autosomal recessive nonsyndromic hearing loss 4 (1)
-	-	1	not provided (1)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.62
CADD	Benign	9.7
DANN	Benign	0.84
PhyloP100		-0.12
PromoterAI		-0.013	Neutral
Mutation Taster		=297/3	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs17154282;

hg19: chr7-107301238;