chr19-48587223-C-G

Variant names:

• chr19-48587223-C-G
• rs199730300
• NM_177973.2:c.215-6C>G

Variant summary

Our verdict is Benign. The variant received -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, 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, intron
• Scores: Splicing: ADA: 0.0004430
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -0.762
• Publications: 0 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: Benign. The variant received -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 VariationId 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 the male GnomAd4 subpopulation. Median coverage is 31. This position passed quality control check.
• BS2: High Homozygotes in GnomAdExome4 at 9 AR gene

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.215-6C>G		splice_region intron	N/A	NP_814444.1	O00204-1
	SULT2B1	NM_004605.2		c.170-6C>G		splice_region intron	N/A	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.215-6C>G		splice_region intron	N/A	ENSP00000201586.2	O00204-1
	SULT2B1	ENST00000323090.4	TSL:1	c.170-6C>G		splice_region intron	N/A	ENSP00000312880.3	O00204-2
	ENSG00000287603	ENST00000666424.1		n.493+9523G>C		intron	N/A

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

GnomAD2 exomes AF: 0.00140 AC: 338 AN: 242012 AF XY: 0.00135

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 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

African (AFR) AF: 0.000270 AC: 9 AN: 33302

American (AMR) AF: 0.000959 AC: 42 AN: 43786

Ashkenazi Jewish (ASJ) AF: 0.0223 AC: 563 AN: 25240

East Asian (EAS) AF: 0.00 AC: 0 AN: 39574

South Asian (SAS) AF: 0.000459 AC: 39 AN: 85008

European-Finnish (FIN) AF: 0.0000189 AC: 1 AN: 52840

Middle Eastern (MID) AF: 0.00929 AC: 53 AN: 5704

European-Non Finnish (NFE) AF: 0.000389 AC: 430 AN: 1105362

Other (OTH) AF: 0.00205 AC: 123 AN: 59862

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

African (AFR) AF: 0.0000963 AC: 4 AN: 41552

American (AMR) AF: 0.000327 AC: 5 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.0222 AC: 77 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5188

South Asian (SAS) AF: 0.000415 AC: 2 AN: 4822

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10610

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.000632 AC: 43 AN: 68032

Other (OTH) AF: 0.000949 AC: 2 AN: 2108

Alfa AF: 0.00291 Hom.: 1

Bravo AF: 0.000963

ClinVar

ClinVar submissions

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	-0.91
CADD	Benign	0.76
DANN	Benign	0.43
PhyloP100		-0.76
Mutation Taster		=100/0	polymorphism

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

Other links and lift over

dbSNP: rs199730300; hg19: chr19-49090480;