chr19-48587223-C-G

Position:

• chr19-48587223-C-G

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

The NM_177973.2(SULT2B1):​c.215-6C>G variant causes a splice region, splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00087 in 1,602,946 control chromosomes in the GnomAD database, including 10 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.00088 (1 hom., cov: 31)
  • Exomes 𝑓: 0.00087 (9 hom.)
• Consequence: SULT2B1 NM_177973.2 splice_region, splice_polypyrimidine_tract, intron
• Scores: Splicing: ADA: 0.0004430
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -0.762

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BP6: Variant 19-48587223-C-G is Benign according to our data. Variant chr19-48587223-C-G is described in ClinVar as [Benign]. Clinvar id is 737863.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.00088 (134/152268) while in subpopulation NFE AF= 0.000632 (43/68032). AF 95% confidence interval is 0.000482. There are 1 homozygotes in gnomad4. There are 51 alleles in male gnomad4 subpopulation. Median coverage is 31. This position pass quality control queck.
• BS2: High Homozygotes in GnomAdExome4 at 9 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SULT2B1	NM_177973.2	c.215-6C>G		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		ENST00000201586.7	NP_814444.1
SULT2B1	NM_004605.2	c.170-6C>G		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant			NP_004596.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SULT2B1	ENST00000201586.7	c.215-6C>G		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		1	NM_177973.2	ENSP00000201586	P2
SULT2B1	ENST00000323090.4	c.170-6C>G		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		1		ENSP00000312880	A2
	ENST00000666424.1	n.493+9523G>C		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.000881 AC: 134 AN: 152150 Hom.: 1 Cov.: 31

Gnomad AFR AF: 0.0000965

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000328

Gnomad ASJ AF: 0.0222

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000414

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.000632

Gnomad OTH AF: 0.000959

GnomAD3 exomes AF: 0.00140 AC: 338 AN: 242012 Hom.: 1 AF XY: 0.00135 AC XY: 177 AN XY: 130884

Gnomad AFR exome AF: 0.000123

Gnomad AMR exome AF: 0.000923

Gnomad ASJ exome AF: 0.0221

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000374

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000572

Gnomad OTH exome AF: 0.00492

GnomAD4 exome AF: 0.000869 AC: 1260 AN: 1450678 Hom.: 9 Cov.: 31 AF XY: 0.000886 AC XY: 638 AN XY: 720370

Gnomad4 AFR exome AF: 0.000270

Gnomad4 AMR exome AF: 0.000959

Gnomad4 ASJ exome AF: 0.0223

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000459

Gnomad4 FIN exome AF: 0.0000189

Gnomad4 NFE exome AF: 0.000389

Gnomad4 OTH exome AF: 0.00205

GnomAD4 genome AF: 0.000880 AC: 134 AN: 152268 Hom.: 1 Cov.: 31 AF XY: 0.000685 AC XY: 51 AN XY: 74460

Gnomad4 AFR AF: 0.0000963

Gnomad4 AMR AF: 0.000327

Gnomad4 ASJ AF: 0.0222

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000415

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000632

Gnomad4 OTH AF: 0.000949

Alfa AF: 0.00291 Hom.: 1

Bravo AF: 0.000963

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Dec 19, 2023	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

SULT2B1-related disorder Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Jul 14, 2020

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.76
DANN	Benign	0.43

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.00044
dbscSNV1_RF	Benign	0.076
SpliceAI score (max)		0.010		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: rs199730300; hg19: chr19-49090480;