rs753586849

Variant names:

• chr7-107695919-AT-A
• rs753586849
• NM_000441.2:c.1438-7delT

Your query was ambiguous. Multiple possible variants found:

• chr7-107695919-AT-A
• chr7-107695919-AT-ATT

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP6_Moderate

The NM_000441.2(SLC26A4):​c.1438-7delT variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000167 in 1,378,118 control chromosomes in the GnomAD database, with no homozygous occurrence. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.000040 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000014 (0 hom.)
• Consequence: SLC26A4 NM_000441.2 splice_region, intron
• Clinical Significance: Benign criteria provided, single submitter U:1 B:1
• Conservation: PhyloP100: 0.859
• Publications: 1 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 Gene-Disease associations (from GenCC):

• autosomal recessive nonsyndromic hearing loss 4

  Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: Ambry Genetics, PanelApp Australia, Labcorp Genetics (formerly Invitae)
• Pendred syndrome

  Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: ClinGen, Ambry Genetics, Orphanet, Labcorp Genetics (formerly Invitae)
• athyreosis

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• thyroid hypoplasia

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• hearing loss, autosomal recessive

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• BP6: Variant 7-107695919-AT-A is Benign according to our data. Variant chr7-107695919-AT-A is described in ClinVar as Benign. ClinVar VariationId is 552885.Status of the report is criteria_provided_single_submitter, 1 stars.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000441.2. 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	NM_000441.2	MANE Select	c.1438-7delT		splice_region intron	N/A	NP_000432.1	O43511-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC26A4	ENST00000644269.2	MANE Select	c.1438-13delT		intron	N/A	ENSP00000494017.1	O43511-1
	SLC26A4	ENST00000888701.1		c.1438-13delT		intron	N/A	ENSP00000558760.1
	SLC26A4	ENST00000888700.1		c.1360-13delT		intron	N/A	ENSP00000558759.1

Frequencies

GnomAD3 genomes AF: 0.0000395 AC: 6 AN: 151736 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000121

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000657

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: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000239 AC: 6 AN: 251154 AF XY: 0.0000221

Gnomad AFR exome AF: 0.0000615

Gnomad AMR exome AF: 0.0000579

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000544

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000176

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000139 AC: 17 AN: 1226382 Hom.: 0 Cov.: 19 AF XY: 0.0000161 AC XY: 10 AN XY: 622604

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.0000696 AC: 2 AN: 28728

American (AMR) AF: 0.0000450 AC: 2 AN: 44402

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24620

East Asian (EAS) AF: 0.0000259 AC: 1 AN: 38614

South Asian (SAS) AF: 0.0000123 AC: 1 AN: 81438

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53314

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5326

European-Non Finnish (NFE) AF: 0.0000123 AC: 11 AN: 897506

Other (OTH) AF: 0.00 AC: 0 AN: 52434

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.0000413319), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome AF: 0.0000395 AC: 6 AN: 151736 Hom.: 0 Cov.: 32 AF XY: 0.0000675 AC XY: 5 AN XY: 74094

African (AFR) AF: 0.000121 AC: 5 AN: 41266

American (AMR) AF: 0.0000657 AC: 1 AN: 15218

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 5184

South Asian (SAS) AF: 0.00 AC: 0 AN: 4816

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10550

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 314

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 67918

Other (OTH) AF: 0.00 AC: 0 AN: 2088

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000416

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)
-	1	-	Pendred syndrome (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.86

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

Other links and lift over

dbSNP: rs753586849; hg19: chr7-107336364; COSMIC: COSV55915963; COSMIC: COSV55915963;