19-48575989-C-T

Variant names:

• chr19-48575989-C-T
• rs2544794
• NM_177973.2:c.120C>T

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_177973.2(SULT2B1):​c.120C>T​(p.Pro40Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.155 in 1,613,536 control chromosomes in the GnomAD database, including 20,560 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.16 (2214 hom., cov: 30)
  • Exomes 𝑓: 0.15 (18346 hom.)
• Consequence: SULT2B1 NM_177973.2 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -2.55
• Publications: 13 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, Genomics England PanelApp, Labcorp Genetics (formerly Invitae), Ambry Genetics, G2P
• lamellar ichthyosis

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ENSG00000287603 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.61).
• BP6: Variant 19-48575989-C-T is Benign according to our data. Variant chr19-48575989-C-T is described in ClinVar as Benign. ClinVar VariationId is 1613054.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-2.55 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.218 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SULT2B1	NM_177973.2	MANE Select	c.120C>T	p.Pro40Pro	synonymous	Exon 2 of 7	NP_814444.1	O00204-1
	SULT2B1	NM_004605.2		c.75C>T	p.Pro25Pro	synonymous	Exon 1 of 6	NP_004596.2	O00204-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SULT2B1	ENST00000201586.7	TSL:1 MANE Select	c.120C>T	p.Pro40Pro	synonymous	Exon 2 of 7	ENSP00000201586.2	O00204-1
	SULT2B1	ENST00000323090.4	TSL:1	c.75C>T	p.Pro25Pro	synonymous	Exon 1 of 6	ENSP00000312880.3	O00204-2
	ENSG00000287603	ENST00000666424.1		n.493+20757G>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.160 AC: 24232 AN: 151884 Hom.: 2214 Cov.: 30

Gnomad AFR AF: 0.222

Gnomad AMI AF: 0.0362

Gnomad AMR AF: 0.106

Gnomad ASJ AF: 0.171

Gnomad EAS AF: 0.00212

Gnomad SAS AF: 0.121

Gnomad FIN AF: 0.106

Gnomad MID AF: 0.108

Gnomad NFE AF: 0.158

Gnomad OTH AF: 0.155

GnomAD2 exomes AF: 0.130 AC: 32296 AN: 248900 AF XY: 0.132

Gnomad AFR exome AF: 0.224

Gnomad AMR exome AF: 0.0720

Gnomad ASJ exome AF: 0.177

Gnomad EAS exome AF: 0.00256

Gnomad FIN exome AF: 0.112

Gnomad NFE exome AF: 0.155

Gnomad OTH exome AF: 0.129

GnomAD4 exome AF: 0.154 AC: 225448 AN: 1461536 Hom.: 18346 Cov.: 32 AF XY: 0.153 AC XY: 111531 AN XY: 727074

African (AFR) AF: 0.223 AC: 7470 AN: 33472

American (AMR) AF: 0.0770 AC: 3443 AN: 44718

Ashkenazi Jewish (ASJ) AF: 0.183 AC: 4771 AN: 26122

East Asian (EAS) AF: 0.000907 AC: 36 AN: 39674

South Asian (SAS) AF: 0.129 AC: 11160 AN: 86238

European-Finnish (FIN) AF: 0.115 AC: 6117 AN: 53400

Middle Eastern (MID) AF: 0.121 AC: 696 AN: 5768

European-Non Finnish (NFE) AF: 0.164 AC: 182382 AN: 1111772

Other (OTH) AF: 0.155 AC: 9373 AN: 60372

GnomAD4 genome AF: 0.160 AC: 24256 AN: 152000 Hom.: 2214 Cov.: 30 AF XY: 0.156 AC XY: 11608 AN XY: 74306

African (AFR) AF: 0.222 AC: 9188 AN: 41428

American (AMR) AF: 0.105 AC: 1607 AN: 15238

Ashkenazi Jewish (ASJ) AF: 0.171 AC: 594 AN: 3472

East Asian (EAS) AF: 0.00213 AC: 11 AN: 5170

South Asian (SAS) AF: 0.121 AC: 581 AN: 4818

European-Finnish (FIN) AF: 0.106 AC: 1121 AN: 10586

Middle Eastern (MID) AF: 0.109 AC: 32 AN: 294

European-Non Finnish (NFE) AF: 0.158 AC: 10766 AN: 67972

Other (OTH) AF: 0.153 AC: 323 AN: 2110

Alfa AF: 0.160 Hom.: 6218

Bravo AF: 0.161

Asia WGS AF: 0.0630 AC: 219 AN: 3478

EpiCase AF: 0.157

EpiControl AF: 0.159

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	1	SULT2B1-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.61
CADD	Benign	2.7
DANN	Benign	0.84
PhyloP100		-2.5
PromoterAI		-0.00080	Neutral
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: rs2544794; hg19: chr19-49079246;