19-48598699-C-T

Variant names:

• chr19-48598699-C-T
• rs4149455
• NM_177973.2:c.827-436C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_177973.2(SULT2B1):​c.827-436C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.414 in 151,792 control chromosomes in the GnomAD database, including 13,721 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.41 (13721 hom., cov: 31)
• Consequence: SULT2B1 NM_177973.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.578
• Publications: 14 publications found

Genes affected

SULT2B1 (HGNC:11459): (sulfotransferase family 2B member 1) Sulfotransferase enzymes catalyze the sulfate conjugation of many hormones, neurotransmitters, drugs, and xenobiotic compounds. These cytosolic enzymes are different in their tissue distributions and substrate specificities. The gene structure (number and length of exons) is similar among family members. This gene sulfates dehydroepiandrosterone but not 4-nitrophenol, a typical substrate for the phenol and estrogen sulfotransferase subfamilies. Two alternatively spliced variants that encode different isoforms have been described. [provided by RefSeq, Jul 2008]

SULT2B1 Gene-Disease associations (from GenCC):

• ichthyosis, congenital, autosomal recessive 14

  Inheritance: AR Classification: STRONG, LIMITED Submitted by: PanelApp Australia, Ambry Genetics, G2P, Labcorp Genetics (formerly Invitae), Genomics England PanelApp
• lamellar ichthyosis

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.536 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_177973.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SULT2B1	NM_177973.2	MANE Select	c.827-436C>T		intron	N/A	NP_814444.1
	SULT2B1	NM_004605.2		c.782-436C>T		intron	N/A	NP_004596.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SULT2B1	ENST00000201586.7	TSL:1 MANE Select	c.827-436C>T		intron	N/A	ENSP00000201586.2
	SULT2B1	ENST00000323090.4	TSL:1	c.782-436C>T		intron	N/A	ENSP00000312880.3
	SULT2B1	ENST00000594274.1	TSL:3	n.577-436C>T		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.414 AC: 62728 AN: 151674 Hom.: 13688 Cov.: 31

Gnomad AFR AF: 0.542

Gnomad AMI AF: 0.411

Gnomad AMR AF: 0.402

Gnomad ASJ AF: 0.309

Gnomad EAS AF: 0.482

Gnomad SAS AF: 0.336

Gnomad FIN AF: 0.464

Gnomad MID AF: 0.188

Gnomad NFE AF: 0.339

Gnomad OTH AF: 0.373

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

GnomAD4 genome AF: 0.414 AC: 62841 AN: 151792 Hom.: 13721 Cov.: 31 AF XY: 0.418 AC XY: 31010 AN XY: 74158

African (AFR) AF: 0.542 AC: 22417 AN: 41346

American (AMR) AF: 0.402 AC: 6134 AN: 15242

Ashkenazi Jewish (ASJ) AF: 0.309 AC: 1073 AN: 3470

East Asian (EAS) AF: 0.482 AC: 2478 AN: 5142

South Asian (SAS) AF: 0.338 AC: 1627 AN: 4820

European-Finnish (FIN) AF: 0.464 AC: 4877 AN: 10516

Middle Eastern (MID) AF: 0.205 AC: 60 AN: 292

European-Non Finnish (NFE) AF: 0.339 AC: 23015 AN: 67946

Other (OTH) AF: 0.373 AC: 786 AN: 2108

Alfa AF: 0.354 Hom.: 16662

Bravo AF: 0.418

Asia WGS AF: 0.414 AC: 1440 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	1.9
DANN	Benign	0.73
PhyloP100		-0.58
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: rs4149455; hg19: chr19-49101956;