chr7-107710094-C-T

Variant names:

• chr7-107710094-C-T
• rs17154347
• NM_000441.2:c.2130C>T

Variant summary

Our verdict is Benign. The variant received -19 ACMG points: 0P and 19B. BP4_Moderate BP6_Very_Strong BP7 BA1

The NM_000441.2(SLC26A4):​c.2130C>T​(p.Asp710Asp) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00369 in 1,611,564 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 Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.019 (78 hom., cov: 32)
  • Exomes 𝑓: 0.0021 (97 hom.)
• Consequence: SLC26A4 NM_000441.2 synonymous
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:11
• Conservation: PhyloP100: -0.234
• 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 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: Benign. The variant received -19 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.3).
• BP6: Variant 7-107710094-C-T is Benign according to our data. Variant chr7-107710094-C-T is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 43538.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-0.234 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0636 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC26A4	NM_000441.2	MANE Select	c.2130C>T	p.Asp710Asp	synonymous	Exon 19 of 21	NP_000432.1	O43511-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC26A4	ENST00000644269.2	MANE Select	c.2130C>T	p.Asp710Asp	synonymous	Exon 19 of 21	ENSP00000494017.1	O43511-1
	SLC26A4	ENST00000888701.1		c.2130C>T	p.Asp710Asp	synonymous	Exon 18 of 20	ENSP00000558760.1
	SLC26A4	ENST00000888700.1		c.2052C>T	p.Asp684Asp	synonymous	Exon 18 of 20	ENSP00000558759.1

Frequencies

GnomAD3 genomes AF: 0.0189 AC: 2877 AN: 152152 Hom.: 78 Cov.: 32

Gnomad AFR AF: 0.0656

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00700

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000620

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000309

Gnomad OTH AF: 0.0134

GnomAD2 exomes AF: 0.00492 AC: 1237 AN: 251266 AF XY: 0.00362

Gnomad AFR exome AF: 0.0663

Gnomad AMR exome AF: 0.00278

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000317

Gnomad OTH exome AF: 0.00343

GnomAD4 exome AF: 0.00210 AC: 3062 AN: 1459294 Hom.: 97 Cov.: 29 AF XY: 0.00179 AC XY: 1302 AN XY: 726174

African (AFR) AF: 0.0706 AC: 2358 AN: 33384

American (AMR) AF: 0.00324 AC: 145 AN: 44708

Ashkenazi Jewish (ASJ) AF: 0.0000383 AC: 1 AN: 26106

East Asian (EAS) AF: 0.0000252 AC: 1 AN: 39674

South Asian (SAS) AF: 0.000267 AC: 23 AN: 86200

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53412

Middle Eastern (MID) AF: 0.00452 AC: 26 AN: 5758

European-Non Finnish (NFE) AF: 0.000189 AC: 210 AN: 1109738

Other (OTH) AF: 0.00494 AC: 298 AN: 60314

GnomAD4 genome AF: 0.0190 AC: 2887 AN: 152270 Hom.: 78 Cov.: 32 AF XY: 0.0180 AC XY: 1341 AN XY: 74452

African (AFR) AF: 0.0657 AC: 2728 AN: 41538

American (AMR) AF: 0.00699 AC: 107 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

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

South Asian (SAS) AF: 0.000621 AC: 3 AN: 4834

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10608

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000309 AC: 21 AN: 68022

Other (OTH) AF: 0.0133 AC: 28 AN: 2112

Alfa AF: 0.00607 Hom.: 20

Bravo AF: 0.0220

Asia WGS AF: 0.00404 AC: 14 AN: 3478

EpiCase AF: 0.000545

EpiControl AF: 0.000296

ClinVar

ClinVar submissions

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.30
CADD	Benign	8.5
DANN	Benign	0.58
PhyloP100		-0.23
Mutation Taster		=100/0	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

Other links and lift over

dbSNP: rs17154347; hg19: chr7-107350539;