rs4808709

Variant names:

• chr19-17891030-A-G
• rs4808709
• NM_000453.3:c.1767+29A>G

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.1767+29A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.233 in 1,442,488 control chromosomes in the GnomAD database, including 41,214 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.22 (4139 hom., cov: 31)
  • Exomes 𝑓: 0.23 (37075 hom.)
• Consequence: SLC5A5 NM_000453.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -0.861
• Publications: 10 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: Ambry Genetics, G2P, 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 19-17891030-A-G is Benign according to our data. Variant chr19-17891030-A-G is described in ClinVar as Benign. ClinVar VariationId is 1222858.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.247 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC5A5	NM_000453.3	c.1767+29A>G		intron_variant	Intron 14 of 14	ENST00000222248.4	NP_000444.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC5A5	ENST00000222248.4	c.1767+29A>G		intron_variant	Intron 14 of 14	1	NM_000453.3	ENSP00000222248.2

Frequencies

GnomAD3 genomes AF: 0.225 AC: 34137 AN: 151924 Hom.: 4132 Cov.: 31

Gnomad AFR AF: 0.219

Gnomad AMI AF: 0.104

Gnomad AMR AF: 0.196

Gnomad ASJ AF: 0.275

Gnomad EAS AF: 0.0121

Gnomad SAS AF: 0.121

Gnomad FIN AF: 0.273

Gnomad MID AF: 0.241

Gnomad NFE AF: 0.250

Gnomad OTH AF: 0.221

GnomAD2 exomes AF: 0.197 AC: 49044 AN: 248472 AF XY: 0.200

Gnomad AFR exome AF: 0.217

Gnomad AMR exome AF: 0.130

Gnomad ASJ exome AF: 0.278

Gnomad EAS exome AF: 0.00669

Gnomad FIN exome AF: 0.261

Gnomad NFE exome AF: 0.246

Gnomad OTH exome AF: 0.214

GnomAD4 exome AF: 0.233 AC: 301246 AN: 1290446 Hom.: 37075 Cov.: 20 AF XY: 0.230 AC XY: 149874 AN XY: 650452

African (AFR) AF: 0.221 AC: 6660 AN: 30096

American (AMR) AF: 0.140 AC: 6210 AN: 44498

Ashkenazi Jewish (ASJ) AF: 0.276 AC: 6919 AN: 25086

East Asian (EAS) AF: 0.0261 AC: 1014 AN: 38816

South Asian (SAS) AF: 0.132 AC: 10944 AN: 82894

European-Finnish (FIN) AF: 0.254 AC: 13543 AN: 53232

Middle Eastern (MID) AF: 0.269 AC: 1453 AN: 5408

European-Non Finnish (NFE) AF: 0.253 AC: 242261 AN: 955686

Other (OTH) AF: 0.224 AC: 12242 AN: 54730

GnomAD4 genome AF: 0.225 AC: 34171 AN: 152042 Hom.: 4139 Cov.: 31 AF XY: 0.222 AC XY: 16511 AN XY: 74324

African (AFR) AF: 0.219 AC: 9071 AN: 41476

American (AMR) AF: 0.196 AC: 2988 AN: 15252

Ashkenazi Jewish (ASJ) AF: 0.275 AC: 954 AN: 3468

East Asian (EAS) AF: 0.0122 AC: 63 AN: 5182

South Asian (SAS) AF: 0.121 AC: 583 AN: 4818

European-Finnish (FIN) AF: 0.273 AC: 2882 AN: 10560

Middle Eastern (MID) AF: 0.245 AC: 72 AN: 294

European-Non Finnish (NFE) AF: 0.250 AC: 16990 AN: 67974

Other (OTH) AF: 0.224 AC: 473 AN: 2108

Alfa AF: 0.238 Hom.: 1666

Bravo AF: 0.219

Asia WGS AF: 0.0960 AC: 334 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Jun 19, 2021

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Thyroid dyshormonogenesis 1 Benign:1

Jul 15, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.98
DANN	Benign	0.66
PhyloP100		-0.86
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: rs4808709; hg19: chr19-18001839; COSMIC: COSV55832655; COSMIC: COSV55832655;