ENST00000398520.6:c.576+4206G>A

Variant names:

• chr4-986922-C-T
• rs116840205
• ENST00000398520.6:c.576+4206G>A

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The ENST00000398520.6(SLC26A1):​c.576+4206G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00368 in 718,066 control chromosomes in the GnomAD database, including 47 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.013 (38 hom., cov: 33)
  • Exomes 𝑓: 0.0011 (9 hom.)
• Consequence: SLC26A1 ENST00000398520.6 intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.214
• Publications: 0 publications found

Genes affected

SLC26A1 (HGNC:10993): (solute carrier family 26 member 1) This gene is a member of a family of sulfate/anion transporter genes. Family members are well conserved in their genomic (number and size of exons) and protein (aa length among species) structures, but have markedly different tissue expression patterns. This gene is primarily expressed in the liver, pancreas, and brain. Three splice variants that encode different isoforms have been identified. [provided by RefSeq, Jul 2008]

IDUA (HGNC:5391): (alpha-L-iduronidase) This gene encodes an enzyme that hydrolyzes the terminal alpha-L-iduronic acid residues of two glycosaminoglycans, dermatan sulfate and heparan sulfate. This hydrolysis is required for the lysosomal degradation of these glycosaminoglycans. Mutations in this gene that result in enzymatic deficiency lead to the autosomal recessive disease mucopolysaccharidosis type I (MPS I). [provided by RefSeq, Jul 2008]

DGKQ (HGNC:2856): (diacylglycerol kinase theta) The protein encoded by this gene contains three cysteine-rich domains, a proline-rich region, and a pleckstrin homology domain with an overlapping Ras-associating domain. It is localized in the speckle domains of the nucleus, and mediates the regeneration of phosphatidylinositol (PI) from diacylglycerol in the PI-cycle during cell signal transduction. [provided by RefSeq, Jul 2008]

ACMG classification

Our verdict: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BP6: Variant 4-986922-C-T is Benign according to our data. Variant chr4-986922-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 1187622.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.0133 (2023/152320) while in subpopulation AFR AF = 0.0454 (1886/41576). AF 95% confidence interval is 0.0437. There are 38 homozygotes in GnomAd4. There are 959 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 38 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IDUA	NM_000203.5	c.-163C>T		upstream_gene_variant		ENST00000514224.2	NP_000194.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IDUA	ENST00000514224.2	c.-163C>T		upstream_gene_variant		2	NM_000203.5	ENSP00000425081.2

Frequencies

GnomAD3 genomes AF: 0.0133 AC: 2024 AN: 152204 Hom.: 37 Cov.: 33

Gnomad AFR AF: 0.0455

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00752

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0127

Gnomad NFE AF: 0.0000588

Gnomad OTH AF: 0.00669

GnomAD4 exome AF: 0.00109 AC: 617 AN: 565746 Hom.: 9 Cov.: 7 AF XY: 0.000857 AC XY: 260 AN XY: 303232

African (AFR) AF: 0.0311 AC: 456 AN: 14658

American (AMR) AF: 0.00248 AC: 82 AN: 33054

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 18108

East Asian (EAS) AF: 0.0000360 AC: 1 AN: 27782

South Asian (SAS) AF: 0.0000797 AC: 5 AN: 62714

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 31670

Middle Eastern (MID) AF: 0.00214 AC: 7 AN: 3270

European-Non Finnish (NFE) AF: 0.0000434 AC: 15 AN: 345634

Other (OTH) AF: 0.00177 AC: 51 AN: 28856

GnomAD4 genome AF: 0.0133 AC: 2023 AN: 152320 Hom.: 38 Cov.: 33 AF XY: 0.0129 AC XY: 959 AN XY: 74478

African (AFR) AF: 0.0454 AC: 1886 AN: 41576

American (AMR) AF: 0.00751 AC: 115 AN: 15314

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

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5180

South Asian (SAS) AF: 0.00 AC: 0 AN: 4830

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10628

Middle Eastern (MID) AF: 0.0102 AC: 3 AN: 294

European-Non Finnish (NFE) AF: 0.0000588 AC: 4 AN: 68000

Other (OTH) AF: 0.00662 AC: 14 AN: 2116

Alfa AF: 0.0112 Hom.: 5

Bravo AF: 0.0145

Asia WGS AF: 0.00173 AC: 6 AN: 3476

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Jul 15, 2018

GeneDx

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	5.0
DANN	Benign	0.82
PhyloP100		-0.21
PromoterAI		0.018	Neutral
RBP_binding_hub_radar		0.85
RBP_regulation_power_radar		3.5
Mutation Taster		=100/0	polymorphism

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs116840205; hg19: chr4-980710;