17-7630105-G-T

Variant names:

• chr17-7630105-G-T
• rs1799941
• ENST00000441599.6:c.-68G>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The ENST00000441599.6(SHBG):​c.-68G>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000166 in 1,207,638 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 32)
  • Exomes 𝑓: 0.0000017 (0 hom.)
• Consequence: SHBG ENST00000441599.6 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.129
• Publications: 0 publications found

Genes affected

SHBG (HGNC:10839): (sex hormone binding globulin) This gene encodes a steroid binding protein that was first described as a plasma protein secreted by the liver but is now thought to participate in the regulation of steroid responses. The encoded protein transports androgens and estrogens in the blood, binding each steroid molecule as a dimer formed from identical or nearly identical monomers. Polymorphisms in this gene have been associated with polycystic ovary syndrome and type 2 diabetes mellitus. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jan 2014]

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000441599.6. 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
	SHBG	NM_001289113.2		c.-63-311G>T		intron	N/A	NP_001276042.1	I3L145
	SHBG	NM_001289114.2		c.-61-313G>T		intron	N/A	NP_001276043.1	I3L145
	SHBG	NM_001289115.2		c.-63-311G>T		intron	N/A	NP_001276044.1	P04278-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SHBG	ENST00000441599.6	TSL:1	c.-68G>T		5_prime_UTR	Exon 1 of 6	ENSP00000393426.2	P04278-4
	SHBG	ENST00000340624.9	TSL:1	c.-63-311G>T		intron	N/A	ENSP00000345675.6	I3L145
	SHBG	ENST00000575314.5	TSL:1	c.-61-313G>T		intron	N/A	ENSP00000458559.1	I3L145

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000166 AC: 2 AN: 1207638 Hom.: 0 Cov.: 17 AF XY: 0.00000163 AC XY: 1 AN XY: 613000

African (AFR) AF: 0.0000352 AC: 1 AN: 28432

American (AMR) AF: 0.00 AC: 0 AN: 44356

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24566

East Asian (EAS) AF: 0.00 AC: 0 AN: 38554

South Asian (SAS) AF: 0.00 AC: 0 AN: 81136

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 48746

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4336

European-Non Finnish (NFE) AF: 0.00000113 AC: 1 AN: 885458

Other (OTH) AF: 0.00 AC: 0 AN: 52054

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.59
DANN	Benign	0.71
PhyloP100		0.13
PromoterAI		-0.051	Neutral

Splicing

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs1799941;

hg19: chr17-7533423;