rs111033440

Variant names:

• chr7-107660670-A-T
• rs111033440
• ENST00000888701.1:c.-972A>T

Your query was ambiguous. Multiple possible variants found:

• chr7-107660670-A-T
• chr7-107660670-A-G

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The ENST00000888701.1(SLC26A4):​c.-972A>T variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000309 in 152,336 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 Uncertain significance (★★). The gene SLC26A4 is included in the ClinGen Criteria Specification Registry.

• Frequency:
  • Genomes: 𝑓 0.00031 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: SLC26A4 ENST00000888701.1 5_prime_UTR_premature_start_codon_gain
• Clinical Significance: Uncertain significance criteria provided, multiple submitters, no conflicts U:5
• Conservation: PhyloP100: -0.109
• Publications: 0 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: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.77).

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.198-464T>A		intron	N/A
	SLC26A4	NM_000441.2	MANE Select	c.-189A>T		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.-972A>T		5_prime_UTR_premature_start_codon_gain	Exon 1 of 20	ENSP00000558760.1
	SLC26A4	ENST00000888701.1		c.-972A>T		5_prime_UTR	Exon 1 of 20	ENSP00000558760.1
	SLC26A4-AS1	ENST00000658036.1		n.1227T>A		non_coding_transcript_exon	Exon 2 of 2

Frequencies

GnomAD3 genomes AF: 0.000309 AC: 47 AN: 152218 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000724

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00144

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000265

Gnomad OTH AF: 0.00191

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 88 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 60

African (AFR) AF: 0.00 AC: 0 AN: 4

American (AMR) AF: 0.00 AC: 0 AN: 2

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 8

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68

Other (OTH) AF: 0.00 AC: 0 AN: 4

GnomAD4 genome AF: 0.000309 AC: 47 AN: 152336 Hom.: 0 Cov.: 32 AF XY: 0.000376 AC XY: 28 AN XY: 74490

African (AFR) AF: 0.0000721 AC: 3 AN: 41584

American (AMR) AF: 0.00144 AC: 22 AN: 15312

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5180

South Asian (SAS) AF: 0.00 AC: 0 AN: 4830

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10620

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 292

European-Non Finnish (NFE) AF: 0.000265 AC: 18 AN: 68024

Other (OTH) AF: 0.00189 AC: 4 AN: 2112

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.000408

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, multiple submitters, no conflicts

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
CADD	Benign	6.8
DANN	Benign	0.78
PhyloP100		-0.11
PromoterAI		-0.031	Neutral

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs111033440;

hg19: chr7-107301115;