chr4-69740308-A-G

Position:

• chr4-69740308-A-G

Variant summary

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

The NM_014465.4(SULT1B1):​c.376-6044T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.613 in 152,058 control chromosomes in the GnomAD database, including 28,684 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as other (no stars).

• Frequency: Genomes: 𝑓 0.61 (28684 hom., cov: 33)
• Consequence: SULT1B1 NM_014465.4 intron
• Clinical Significance: other no assertion criteria provided O:1
• Conservation: PhyloP100: -0.888

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.7 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SULT1B1	NM_014465.4	c.376-6044T>C		intron_variant		ENST00000310613.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SULT1B1	ENST00000310613.8	c.376-6044T>C		intron_variant		1	NM_014465.4	P1
SULT1B1	ENST00000510821.1	c.376-6044T>C		intron_variant		3

Frequencies

GnomAD3 genomes AF: 0.613 AC: 93076 AN: 151940 Hom.: 28660 Cov.: 33

Gnomad AFR AF: 0.581

Gnomad AMI AF: 0.648

Gnomad AMR AF: 0.604

Gnomad ASJ AF: 0.572

Gnomad EAS AF: 0.719

Gnomad SAS AF: 0.651

Gnomad FIN AF: 0.680

Gnomad MID AF: 0.612

Gnomad NFE AF: 0.614

Gnomad OTH AF: 0.605

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.613 AC: 93151 AN: 152058 Hom.: 28684 Cov.: 33 AF XY: 0.616 AC XY: 45771 AN XY: 74346

Gnomad4 AFR AF: 0.582

Gnomad4 AMR AF: 0.604

Gnomad4 ASJ AF: 0.572

Gnomad4 EAS AF: 0.719

Gnomad4 SAS AF: 0.651

Gnomad4 FIN AF: 0.680

Gnomad4 NFE AF: 0.614

Gnomad4 OTH AF: 0.600

Alfa AF: 0.608 Hom.: 5188

Bravo AF: 0.609

Asia WGS AF: 0.627 AC: 2183 AN: 3478

ClinVar

Significance: other

Submissions summary: Other:1

Revision: no assertion criteria provided

Submissions by phenotype

Levothyroxine response Other:1

other, no assertion criteria provided

research

Pharmacogenomics/Precision medicine lab, University of Petra

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- in initial analysis the (AA) genotype was associated with higher TSH levels. BMI levels were also affected by the rs11249460 in this gene in the same direction in the initial analysis. After correction for multiple testing both were not statistically significant.

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	1.7
DANN	Benign	0.81

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		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: rs11249460; hg19: chr4-70606026;