Genetic Variant SULT1A1:c.-4-392G>A (chr16-28609251-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001055.4(SULT1A1):c.-4-392G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.47 in 1,242,994 control chromosomes in the GnomAD database, including 134,960 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 0.45 ( 14814 hom., cov: 38)

Exomes 𝑓: 0.47 ( 120146 hom. )

Consequence

SULT1A1
NM_001055.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.336

Publications

29 publications found

Variant links:

Genes affected

SULT1A1 (HGNC:11453): (sulfotransferase family 1A 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 one of two phenol sulfotransferases with thermostable enzyme activity. Multiple alternatively spliced variants that encode two isoforms have been identified for this gene. [provided by RefSeq, Jul 2008]

SULT1A1 links:

ENSG00000289755 (HGNC:):

ENSG00000289755 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-1.01).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.49 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001055.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
SULT1A1	NM_001055.4	MANE Select	c.-4-392G>A	intron	N/A	NP_001046.2
SULT1A1	NM_001394422.1		c.-197G>A	5_prime_UTR_premature_start_codon_gain	Exon 3 of 10	NP_001381351.1
SULT1A1	NM_177530.4		c.-197G>A	5_prime_UTR_premature_start_codon_gain	Exon 1 of 8	NP_803566.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
SULT1A1	ENST00000314752.12	TSL:1 MANE Select	c.-4-392G>A	intron	N/A	ENSP00000321988.7
ENSG00000289755	ENST00000562058.5	TSL:1	n.756-392G>A	intron	N/A
ENSG00000289755	ENST00000564818.5	TSL:1	n.527+112G>A	intron	N/A

Frequencies

GnomAD3 genomes

AF:

0.449

AC:

67576

AN:

150432

Hom.:

14796

Cov.:

show subpopulations

Gnomad AFR

AF:

0.356

Gnomad AMI

AF:

0.417

Gnomad AMR

AF:

0.481

Gnomad ASJ

AF:

0.410

Gnomad EAS

AF:

0.441

Gnomad SAS

AF:

0.308

Gnomad FIN

AF:

0.571

Gnomad MID

AF:

0.342

Gnomad NFE

AF:

0.494

Gnomad OTH

AF:

0.421

GnomAD4 exome

AF:

0.473

AC:

517035

AN:

1092444

Hom.:

120146

Cov.:

AF XY:

0.469

AC XY:

247950

AN XY:

528860

show subpopulations

African (AFR)

AF:

0.341

AC:

8246

AN:

24148

American (AMR)

AF:

0.534

AC:

8529

AN:

15980

Ashkenazi Jewish (ASJ)

AF:

0.407

AC:

5106

AN:

12548

East Asian (EAS)

AF:

0.462

AC:

7652

AN:

16558

South Asian (SAS)

AF:

0.316

AC:

19973

AN:

63164

European-Finnish (FIN)

AF:

0.558

AC:

6846

AN:

12266

Middle Eastern (MID)

AF:

0.366

AC:

1100

AN:

3006

European-Non Finnish (NFE)

AF:

0.488

AC:

440899

AN:

903900

Other (OTH)

AF:

0.457

AC:

18684

AN:

40874

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.459

Heterozygous variant carriers

11307

22614

33920

45227

56534

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

15114

30228

45342

60456

75570

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.449

AC:

67648

AN:

150550

Hom.:

14814

Cov.:

AF XY:

0.451

AC XY:

33161

AN XY:

73544

show subpopulations

African (AFR)

AF:

0.356

AC:

14585

AN:

40932

American (AMR)

AF:

0.482

AC:

7267

AN:

15086

Ashkenazi Jewish (ASJ)

AF:

0.410

AC:

1419

AN:

3458

East Asian (EAS)

AF:

0.441

AC:

2256

AN:

5118

South Asian (SAS)

AF:

0.308

AC:

1466

AN:

4764

European-Finnish (FIN)

AF:

0.571

AC:

5989

AN:

10496

Middle Eastern (MID)

AF:

0.337

AC:

AN:

288

European-Non Finnish (NFE)

AF:

0.494

AC:

33315

AN:

67432

Other (OTH)

AF:

0.423

AC:

876

AN:

2070

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.497

Heterozygous variant carriers

1242

2484

3727

4969

6211

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

648

1296

1944

2592

3240

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.315

Hom.:

685

Asia WGS

AF:

0.396

AC:

1375

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-1.0

CADD

Benign

2.2

(source)

DANN

Benign

0.50

PhyloP100

-0.34

PromoterAI

-0.10

Neutral

(source)

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over