19-48576007-C-T

Variant names:

• chr19-48576007-C-T
• rs571347276
• NM_177973.2:c.138C>T

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 2P and 7B. PM2 BP4_Strong BP6_Moderate BP7

The NM_177973.2(SULT2B1):​c.138C>T​(p.Leu46Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000434 in 1,613,858 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0000066 (0 hom., cov: 30)
  • Exomes 𝑓: 0.0000041 (0 hom.)
• Consequence: SULT2B1 NM_177973.2 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -9.24
• Publications: 1 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: G2P, Genomics England PanelApp, Labcorp Genetics (formerly Invitae), PanelApp Australia, Ambry Genetics
• lamellar ichthyosis

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ENSG00000287603 (HGNC:):

ACMG classification

Our verdict: Likely_benign. The variant received -5 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BP6: Variant 19-48576007-C-T is Benign according to our data. Variant chr19-48576007-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 2976267.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-9.24 with no splicing effect.

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.138C>T	p.Leu46Leu	synonymous	Exon 2 of 7	NP_814444.1	O00204-1
	SULT2B1	NM_004605.2		c.93C>T	p.Leu31Leu	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.138C>T	p.Leu46Leu	synonymous	Exon 2 of 7	ENSP00000201586.2	O00204-1
	SULT2B1	ENST00000323090.4	TSL:1	c.93C>T	p.Leu31Leu	synonymous	Exon 1 of 6	ENSP00000312880.3	O00204-2
	ENSG00000287603	ENST00000666424.1		n.493+20739G>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.00000658 AC: 1 AN: 152050 Hom.: 0 Cov.: 30

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.00000402 AC: 1 AN: 248994 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000898

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000410 AC: 6 AN: 1461808 Hom.: 0 Cov.: 32 AF XY: 0.00000275 AC XY: 2 AN XY: 727208

African (AFR) AF: 0.00 AC: 0 AN: 33478

American (AMR) AF: 0.0000224 AC: 1 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26132

East Asian (EAS) AF: 0.00 AC: 0 AN: 39698

South Asian (SAS) AF: 0.00 AC: 0 AN: 86252

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53406

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5766

European-Non Finnish (NFE) AF: 0.00000450 AC: 5 AN: 1111960

Other (OTH) AF: 0.00 AC: 0 AN: 60392

GnomAD4 genome AF: 0.00000658 AC: 1 AN: 152050 Hom.: 0 Cov.: 30 AF XY: 0.0000135 AC XY: 1 AN XY: 74264

African (AFR) AF: 0.00 AC: 0 AN: 41402

American (AMR) AF: 0.00 AC: 0 AN: 15232

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5180

South Asian (SAS) AF: 0.00 AC: 0 AN: 4832

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10594

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 68022

Other (OTH) AF: 0.00 AC: 0 AN: 2090

Alfa AF: 0.0000534 Hom.: 0

Bravo AF: 0.0000113

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.15
DANN	Benign	0.72
PhyloP100		-9.2
PromoterAI		-0.017	Neutral

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: rs571347276; hg19: chr19-49079264; COSMIC: COSV52378329;