rs7250346

Variant names:

• chr19-17893553-C-G
• rs7250346
• NM_000453.3:c.1768-160C>G

Your query was ambiguous. Multiple possible variants found:

• chr19-17893553-C-G
• chr19-17893553-C-A
• chr19-17893553-C-T

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.1768-160C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.327 in 151,928 control chromosomes in the GnomAD database, including 10,306 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency: Genomes: 𝑓 0.33 (10306 hom., cov: 31)
• Consequence: SLC5A5 NM_000453.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.0770
• Publications: 5 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=-1.0).
• BP6: Variant 19-17893553-C-G is Benign according to our data. Variant chr19-17893553-C-G is described in ClinVar as Benign. ClinVar VariationId is 1231310.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.576 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.1768-160C>G		intron	N/A	NP_000444.1	Q92911
	SLC5A5	NM_001440707.1		c.1501-160C>G		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.1768-160C>G		intron	N/A	ENSP00000222248.2	Q92911

Frequencies

GnomAD3 genomes AF: 0.326 AC: 49512 AN: 151810 Hom.: 10267 Cov.: 31

Gnomad AFR AF: 0.582

Gnomad AMI AF: 0.104

Gnomad AMR AF: 0.234

Gnomad ASJ AF: 0.285

Gnomad EAS AF: 0.0118

Gnomad SAS AF: 0.114

Gnomad FIN AF: 0.273

Gnomad MID AF: 0.268

Gnomad NFE AF: 0.245

Gnomad OTH AF: 0.294

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

GnomAD4 genome AF: 0.327 AC: 49608 AN: 151928 Hom.: 10306 Cov.: 31 AF XY: 0.320 AC XY: 23734 AN XY: 74266

African (AFR) AF: 0.582 AC: 24102 AN: 41388

American (AMR) AF: 0.234 AC: 3562 AN: 15242

Ashkenazi Jewish (ASJ) AF: 0.285 AC: 989 AN: 3472

East Asian (EAS) AF: 0.0118 AC: 61 AN: 5172

South Asian (SAS) AF: 0.113 AC: 546 AN: 4822

European-Finnish (FIN) AF: 0.273 AC: 2885 AN: 10558

Middle Eastern (MID) AF: 0.274 AC: 80 AN: 292

European-Non Finnish (NFE) AF: 0.245 AC: 16664 AN: 67964

Other (OTH) AF: 0.296 AC: 624 AN: 2106

Alfa AF: 0.160 Hom.: 325

Bravo AF: 0.336

Asia WGS AF: 0.119 AC: 413 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	4.1
DANN	Benign	0.69
PhyloP100		0.077
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: rs7250346; hg19: chr19-18004362;