Variant rs4808709 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

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

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -0.861

Variant links:

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 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -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 id 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/exons	MANE	Protein	UniProt
SLC5A5	NM_000453.3 linkuse as main transcript	c.1767+29A>G		intron_variant		ENST00000222248.4	NP_000444.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLC5A5	ENST00000222248.4 linkuse as main transcript	c.1767+29A>G		intron_variant		1	NM_000453.3	ENSP00000222248	P1

Frequencies

GnomAD3 genomes

AF:

0.225

AC:

34137

AN:

151924

Hom.:

4132

Cov.:

show subpopulations

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

GnomAD3 exomes

AF:

0.197

AC:

49044

AN:

248472

Hom.:

5756

AF XY:

0.200

AC XY:

26841

AN XY:

134504

show subpopulations

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 SAS exome

AF:

0.125

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.:

AF XY:

0.230

AC XY:

149874

AN XY:

650452

show subpopulations

Gnomad4 AFR exome

AF:

0.221

Gnomad4 AMR exome

AF:

0.140

Gnomad4 ASJ exome

AF:

0.276

Gnomad4 EAS exome

AF:

0.0261

Gnomad4 SAS exome

AF:

0.132

Gnomad4 FIN exome

AF:

0.254

Gnomad4 NFE exome

AF:

0.253

Gnomad4 OTH exome

AF:

0.224

GnomAD4 genome

AF:

0.225

AC:

34171

AN:

152042

Hom.:

4139

Cov.:

AF XY:

0.222

AC XY:

16511

AN XY:

74324

show subpopulations

Gnomad4 AFR

AF:

0.219

Gnomad4 AMR

AF:

0.196

Gnomad4 ASJ

AF:

0.275

Gnomad4 EAS

AF:

0.0122

Gnomad4 SAS

AF:

0.121

Gnomad4 FIN

AF:

0.273

Gnomad4 NFE

AF:

0.250

Gnomad4 OTH

AF:

0.224

Alfa

AF:

0.236

Hom.:

1032

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

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 19, 2021	- -

Thyroid dyshormonogenesis 1

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 15, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.87

CADD

Benign

0.98

DANN

Benign

0.66

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over