chr4-69847802-G-C

Position:

• chr4-69847802-G-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_005420.3(SULT1E1):​c.497-10C>G variant causes a splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.116 in 1,583,348 control chromosomes in the GnomAD database, including 11,928 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.12 (1151 hom., cov: 32)
  • Exomes 𝑓: 0.12 (10777 hom.)
• Consequence: SULT1E1 NM_005420.3 splice_polypyrimidine_tract, intron
• Scores: Splicing: ADA: 0.006855
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.100

Genes affected

SULT1E1 (HGNC:11377): (sulfotransferase family 1E 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 encodes a protein that transfers a sulfo moiety to and from estrone, which may control levels of estrogen receptors. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.65).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.124 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SULT1E1	NM_005420.3	c.497-10C>G		splice_polypyrimidine_tract_variant, intron_variant		ENST00000226444.4	NP_005411.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SULT1E1	ENST00000226444.4	c.497-10C>G		splice_polypyrimidine_tract_variant, intron_variant		1	NM_005420.3	ENSP00000226444	P1

Frequencies

GnomAD3 genomes AF: 0.116 AC: 17518 AN: 151238 Hom.: 1149 Cov.: 32

Gnomad AFR AF: 0.0954

Gnomad AMI AF: 0.0945

Gnomad AMR AF: 0.0891

Gnomad ASJ AF: 0.161

Gnomad EAS AF: 0.000773

Gnomad SAS AF: 0.0467

Gnomad FIN AF: 0.240

Gnomad MID AF: 0.178

Gnomad NFE AF: 0.126

Gnomad OTH AF: 0.125

GnomAD3 exomes AF: 0.108 AC: 26451 AN: 245216 Hom.: 1878 AF XY: 0.108 AC XY: 14400 AN XY: 132770

Gnomad AFR exome AF: 0.0923

Gnomad AMR exome AF: 0.0591

Gnomad ASJ exome AF: 0.161

Gnomad EAS exome AF: 0.000111

Gnomad SAS exome AF: 0.0452

Gnomad FIN exome AF: 0.227

Gnomad NFE exome AF: 0.131

Gnomad OTH exome AF: 0.121

GnomAD4 exome AF: 0.116 AC: 166284 AN: 1431992 Hom.: 10777 Cov.: 24 AF XY: 0.115 AC XY: 82013 AN XY: 713576

Gnomad4 AFR exome AF: 0.0959

Gnomad4 AMR exome AF: 0.0645

Gnomad4 ASJ exome AF: 0.163

Gnomad4 EAS exome AF: 0.000307

Gnomad4 SAS exome AF: 0.0469

Gnomad4 FIN exome AF: 0.224

Gnomad4 NFE exome AF: 0.122

Gnomad4 OTH exome AF: 0.117

GnomAD4 genome AF: 0.116 AC: 17531 AN: 151356 Hom.: 1151 Cov.: 32 AF XY: 0.118 AC XY: 8752 AN XY: 73958

Gnomad4 AFR AF: 0.0955

Gnomad4 AMR AF: 0.0891

Gnomad4 ASJ AF: 0.161

Gnomad4 EAS AF: 0.000775

Gnomad4 SAS AF: 0.0463

Gnomad4 FIN AF: 0.240

Gnomad4 NFE AF: 0.126

Gnomad4 OTH AF: 0.124

Alfa AF: 0.126 Hom.: 234

Bravo AF: 0.106

Asia WGS AF: 0.0310 AC: 107 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.65
CADD	Benign	9.3
DANN	Benign	0.70

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.0069
dbscSNV1_RF	Benign	0.14
SpliceAI score (max)		0.19		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: rs1220702; hg19: chr4-70713520;