rs2188561

Variant names:

• chr7-107695613-C-A
• rs2188561
• NM_000441.2:c.1438-320C>A

Your query was ambiguous. Multiple possible variants found:

• chr7-107695613-C-A
• chr7-107695613-C-T

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_000441.2(SLC26A4):​c.1438-320C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.193 in 151,992 control chromosomes in the GnomAD database, including 3,602 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.19 (3602 hom., cov: 32)
• Consequence: SLC26A4 NM_000441.2 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -3.24
• Publications: 8 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: Ambry Genetics, Orphanet, Labcorp Genetics (formerly Invitae), ClinGen
• 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: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.09).
• BP6: Variant 7-107695613-C-A is Benign according to our data. Variant chr7-107695613-C-A is described in ClinVar as Benign. ClinVar VariationId is 1225871.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.4 is higher than 0.05.

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC26A4	NM_000441.2	MANE Select	c.1438-320C>A		intron	N/A	NP_000432.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC26A4	ENST00000644269.2	MANE Select	c.1438-320C>A		intron	N/A	ENSP00000494017.1
	SLC26A4	ENST00000460748.1	TSL:4	n.541-320C>A		intron	N/A
	SLC26A4	ENST00000477350.5	TSL:4	n.285-320C>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.193 AC: 29256 AN: 151874 Hom.: 3600 Cov.: 32

Gnomad AFR AF: 0.0473

Gnomad AMI AF: 0.181

Gnomad AMR AF: 0.281

Gnomad ASJ AF: 0.220

Gnomad EAS AF: 0.355

Gnomad SAS AF: 0.416

Gnomad FIN AF: 0.278

Gnomad MID AF: 0.244

Gnomad NFE AF: 0.218

Gnomad OTH AF: 0.197

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.193 AC: 29268 AN: 151992 Hom.: 3602 Cov.: 32 AF XY: 0.204 AC XY: 15131 AN XY: 74280

African (AFR) AF: 0.0471 AC: 1954 AN: 41486

American (AMR) AF: 0.281 AC: 4290 AN: 15242

Ashkenazi Jewish (ASJ) AF: 0.220 AC: 763 AN: 3468

East Asian (EAS) AF: 0.355 AC: 1838 AN: 5174

South Asian (SAS) AF: 0.416 AC: 2001 AN: 4814

European-Finnish (FIN) AF: 0.278 AC: 2932 AN: 10542

Middle Eastern (MID) AF: 0.235 AC: 69 AN: 294

European-Non Finnish (NFE) AF: 0.218 AC: 14831 AN: 67952

Other (OTH) AF: 0.202 AC: 425 AN: 2108

Alfa AF: 0.0783 Hom.: 101

Bravo AF: 0.183

Asia WGS AF: 0.374 AC: 1296 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, single submitter

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.1
CADD	Benign	0.084
DANN	Benign	0.34
PhyloP100		-3.2
Mutation Taster		=100/0	polymorphism (auto)

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: rs2188561; hg19: chr7-107336058;