19-48552267-C-T

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BS1 BS2

The NM_177973.2(SULT2B1):c.15C>T(p.Ala5=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00621 in 1,613,932 control chromosomes in the GnomAD database, including 50 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0047 (1 hom., cov: 32)
  • Exomes 𝑓: 0.0064 (49 hom.)
• Consequence: SULT2B1 NM_177973.2 synonymous
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.03

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]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BP6: Variant 19-48552267-C-T is Benign according to our data. Variant chr19-48552267-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 711605.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-1.03 with no splicing effect.
• BS1: Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.00467 (711/152310) while in subpopulation SAS AF= 0.00745 (36/4830). AF 95% confidence interval is 0.00685. There are 1 homozygotes in gnomad4. There are 351 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAdExome at 5 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SULT2B1	NM_177973.2	c.15C>T	p.Ala5=	synonymous_variant	1/7	ENST00000201586.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SULT2B1	ENST00000201586.7	c.15C>T	p.Ala5=	synonymous_variant	1/7	1	NM_177973.2	P2
	ENST00000666424.1	n.494-1734G>A		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.00468 AC: 712 AN: 152192 Hom.: 1 Cov.: 32

Gnomad AFR AF: 0.000917

Gnomad AMI AF: 0.0760

Gnomad AMR AF: 0.00124

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000385

Gnomad SAS AF: 0.00765

Gnomad FIN AF: 0.00358

Gnomad MID AF: 0.00949

Gnomad NFE AF: 0.00738

Gnomad OTH AF: 0.00191

GnomAD3 exomes AF: 0.00489 AC: 1219 AN: 249374 Hom.: 5 AF XY: 0.00544 AC XY: 736 AN XY: 135174

Gnomad AFR exome AF: 0.00138

Gnomad AMR exome AF: 0.00157

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0103

Gnomad FIN exome AF: 0.00258

Gnomad NFE exome AF: 0.00669

Gnomad OTH exome AF: 0.00328

GnomAD4 exome AF: 0.00637 AC: 9309 AN: 1461622 Hom.: 49 Cov.: 31 AF XY: 0.00649 AC XY: 4716 AN XY: 727128

Gnomad4 AFR exome AF: 0.00137

Gnomad4 AMR exome AF: 0.00141

Gnomad4 ASJ exome AF: 0.000115

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0103

Gnomad4 FIN exome AF: 0.00223

Gnomad4 NFE exome AF: 0.00709

Gnomad4 OTH exome AF: 0.00424

GnomAD4 genome AF: 0.00467 AC: 711 AN: 152310 Hom.: 1 Cov.: 32 AF XY: 0.00471 AC XY: 351 AN XY: 74472

Gnomad4 AFR AF: 0.000914

Gnomad4 AMR AF: 0.00124

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.000386

Gnomad4 SAS AF: 0.00745

Gnomad4 FIN AF: 0.00358

Gnomad4 NFE AF: 0.00738

Gnomad4 OTH AF: 0.00189

Alfa AF: 0.00546 Hom.: 5

Bravo AF: 0.00433

Asia WGS AF: 0.00173 AC: 6 AN: 3478

EpiCase AF: 0.00622

EpiControl AF: 0.00717

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Likely benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Feb 01, 2024	SULT2B1: BP4, BP7, BS2 -
Benign, criteria provided, single submitter	clinical testing	Invitae	Dec 28, 2023	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
Cadd	Benign	0.68
Dann	Benign	0.64

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

Publications

LitVar

Other links and lift over

dbSNP: rs16982141; hg19: chr19-49055524; COSMIC: COSV105855098;