chr4-69754675-G-A

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_ModerateBP6_Moderate

The NM_014465.4(SULT1B1):​c.272C>T​(p.Thr91Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000992 in 1,612,192 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.000039 ( 0 hom., cov: 33)
Exomes 𝑓: 0.0000068 ( 0 hom. )

Consequence

SULT1B1
NM_014465.4 missense

Scores

19

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.228
Variant links:
Genes affected
SULT1B1 (HGNC:17845): (sulfotransferase family 1B 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. However, the total genomic length of this gene is greater than that of other SULT1 genes. [provided by RefSeq, Jul 2008]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.08809662).
BP6
Variant 4-69754675-G-A is Benign according to our data. Variant chr4-69754675-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 3172050.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
SULT1B1NM_014465.4 linkuse as main transcriptc.272C>T p.Thr91Ile missense_variant 3/8 ENST00000310613.8

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
SULT1B1ENST00000310613.8 linkuse as main transcriptc.272C>T p.Thr91Ile missense_variant 3/81 NM_014465.4 P1
SULT1B1ENST00000510821.1 linkuse as main transcriptc.272C>T p.Thr91Ile missense_variant 4/63
SULT1B1ENST00000512870.1 linkuse as main transcriptc.215C>T p.Thr72Ile missense_variant 5/53

Frequencies

GnomAD3 genomes
AF:
0.0000395
AC:
6
AN:
152066
Hom.:
0
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.0000241
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.000262
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00
Gnomad OTH
AF:
0.000478
GnomAD3 exomes
AF:
0.00000799
AC:
2
AN:
250182
Hom.:
0
AF XY:
0.00000739
AC XY:
1
AN XY:
135304
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.0000582
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000685
AC:
10
AN:
1460126
Hom.:
0
Cov.:
31
AF XY:
0.00000964
AC XY:
7
AN XY:
726340
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.0000898
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000270
Gnomad4 OTH exome
AF:
0.0000497
GnomAD4 genome
AF:
0.0000395
AC:
6
AN:
152066
Hom.:
0
Cov.:
33
AF XY:
0.0000404
AC XY:
3
AN XY:
74276
show subpopulations
Gnomad4 AFR
AF:
0.0000241
Gnomad4 AMR
AF:
0.000262
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.000478
Alfa
AF:
0.0000712
Hom.:
0
Bravo
AF:
0.000151

ClinVar

Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Benign:1
Likely benign, criteria provided, single submitterclinical testingAmbry GeneticsJan 02, 2024This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.11
BayesDel_addAF
Benign
-0.23
T
BayesDel_noAF
Benign
-0.39
CADD
Benign
0.016
DANN
Benign
0.51
DEOGEN2
Benign
0.10
T;.;T
Eigen
Benign
-1.3
Eigen_PC
Benign
-1.3
FATHMM_MKL
Benign
0.013
N
LIST_S2
Benign
0.23
T;T;T
M_CAP
Benign
0.011
T
MetaRNN
Benign
0.088
T;T;T
MetaSVM
Benign
-0.94
T
MutationAssessor
Benign
0.36
N;.;.
MutationTaster
Benign
1.0
N
PrimateAI
Benign
0.32
T
PROVEAN
Benign
-0.67
N;N;N
REVEL
Benign
0.035
Sift
Benign
0.29
T;T;T
Sift4G
Benign
0.28
T;.;.
Polyphen
0.0
B;.;.
Vest4
0.10
MutPred
0.38
Loss of disorder (P = 0.0338);Loss of disorder (P = 0.0338);.;
MVP
0.41
MPC
0.015
ClinPred
0.016
T
GERP RS
-1.5
Varity_R
0.041
gMVP
0.35

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.020
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

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs1033246300; hg19: chr4-70620393; API