rs4808708

Variant names:

• chr19-17890877-G-A
• rs4808708
• NM_000453.3:c.1652-9G>A

Variant summary

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

The NM_000453.3(SLC5A5):​c.1652-9G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.214 in 1,597,824 control chromosomes in the GnomAD database, including 38,849 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.19 (3029 hom., cov: 31)
  • Exomes 𝑓: 0.22 (35820 hom.)
• Consequence: SLC5A5 NM_000453.3 intron
• Scores: Splicing: ADA: 0.00005823
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:8
• Conservation: PhyloP100: -0.00600
• Publications: 12 publications found

Genes affected

SLC5A5 (HGNC:11040): (solute carrier family 5 member 5) This gene encodes a member of the sodium glucose cotransporter family. The encoded protein is responsible for the uptake of iodine in tissues such as the thyroid and lactating breast tissue. The iodine taken up by the thyroid is incorporated into the metabolic regulators triiodothyronine (T3) and tetraiodothyronine (T4). Mutations in this gene are associated with thyroid dyshormonogenesis 1.[provided by RefSeq, Sep 2009]

SLC5A5 Gene-Disease associations (from GenCC):

• thyroid dyshormonogenesis 1

  Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: G2P, PanelApp Australia, Ambry Genetics, Labcorp Genetics (formerly Invitae)
• familial thyroid dyshormonogenesis

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BP6: Variant 19-17890877-G-A is Benign according to our data. Variant chr19-17890877-G-A is described in ClinVar as Benign. ClinVar VariationId is 256199.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.232 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000453.3. 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
	SLC5A5	NM_000453.3	MANE Select	c.1652-9G>A		intron	N/A	NP_000444.1	Q92911
	SLC5A5	NM_001440707.1		c.1385-9G>A		intron	N/A	NP_001427636.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC5A5	ENST00000222248.4	TSL:1 MANE Select	c.1652-9G>A		intron	N/A	ENSP00000222248.2	Q92911

Frequencies

GnomAD3 genomes AF: 0.187 AC: 28314 AN: 151740 Hom.: 3026 Cov.: 31

Gnomad AFR AF: 0.122

Gnomad AMI AF: 0.0945

Gnomad AMR AF: 0.167

Gnomad ASJ AF: 0.236

Gnomad EAS AF: 0.0118

Gnomad SAS AF: 0.120

Gnomad FIN AF: 0.265

Gnomad MID AF: 0.231

Gnomad NFE AF: 0.235

Gnomad OTH AF: 0.186

GnomAD2 exomes AF: 0.179 AC: 44669 AN: 249144 AF XY: 0.183

Gnomad AFR exome AF: 0.121

Gnomad AMR exome AF: 0.114

Gnomad ASJ exome AF: 0.234

Gnomad EAS exome AF: 0.00669

Gnomad FIN exome AF: 0.254

Gnomad NFE exome AF: 0.231

Gnomad OTH exome AF: 0.196

GnomAD4 exome AF: 0.216 AC: 312877 AN: 1445966 Hom.: 35820 Cov.: 29 AF XY: 0.214 AC XY: 154331 AN XY: 720230

African (AFR) AF: 0.123 AC: 4069 AN: 33150

American (AMR) AF: 0.122 AC: 5449 AN: 44702

Ashkenazi Jewish (ASJ) AF: 0.232 AC: 6034 AN: 26036

East Asian (EAS) AF: 0.0258 AC: 1023 AN: 39628

South Asian (SAS) AF: 0.130 AC: 11177 AN: 85910

European-Finnish (FIN) AF: 0.246 AC: 13143 AN: 53358

Middle Eastern (MID) AF: 0.256 AC: 1363 AN: 5314

European-Non Finnish (NFE) AF: 0.235 AC: 258556 AN: 1098012

Other (OTH) AF: 0.202 AC: 12063 AN: 59856

GnomAD4 genome AF: 0.187 AC: 28336 AN: 151858 Hom.: 3029 Cov.: 31 AF XY: 0.185 AC XY: 13735 AN XY: 74190

African (AFR) AF: 0.122 AC: 5039 AN: 41422

American (AMR) AF: 0.167 AC: 2540 AN: 15226

Ashkenazi Jewish (ASJ) AF: 0.236 AC: 820 AN: 3468

East Asian (EAS) AF: 0.0118 AC: 61 AN: 5168

South Asian (SAS) AF: 0.121 AC: 580 AN: 4810

European-Finnish (FIN) AF: 0.265 AC: 2795 AN: 10528

Middle Eastern (MID) AF: 0.238 AC: 70 AN: 294

European-Non Finnish (NFE) AF: 0.235 AC: 15945 AN: 67922

Other (OTH) AF: 0.190 AC: 400 AN: 2110

Alfa AF: 0.218 Hom.: 5542

Bravo AF: 0.176

Asia WGS AF: 0.0890 AC: 309 AN: 3478

EpiCase AF: 0.237

EpiControl AF: 0.236

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	not provided (3)
-	-	3	Thyroid dyshormonogenesis 1 (3)
-	-	2	not specified (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	2.7
DANN	Benign	0.62
PhyloP100		-0.0060
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.000058
dbscSNV1_RF	Benign	0.0
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: rs4808708; hg19: chr19-18001686;