rs8023023

Variant names:

• chr14-94307539-G-A
• rs8023023
• NM_001756.4:c.885-1321C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001756.4(SERPINA6):​c.885-1321C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.474 in 152,138 control chromosomes in the GnomAD database, including 18,291 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 0.47 (18291 hom., cov: 34)
• Consequence: SERPINA6 NM_001756.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.15
• Publications: 4 publications found

Genes affected

SERPINA6 (HGNC:1540): (serpin family A member 6) This gene encodes an alpha-globulin protein with corticosteroid-binding properties. This is the major transport protein for glucorticoids and progestins in the blood of most vertebrates. The gene localizes to a chromosomal region containing several closely related serine protease inhibitors which may have evolved by duplication events. [provided by RefSeq, Jul 2008]

SERPINA6 Gene-Disease associations (from GenCC):

• corticosteroid-binding globulin deficiency

  Inheritance: AR, AD, SD, Unknown Classification: STRONG, MODERATE, SUPPORTIVE, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics, PanelApp Australia, Orphanet

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.905 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001756.4. 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
	SERPINA6	NM_001756.4	MANE Select	c.885-1321C>T		intron	N/A	NP_001747.3	P08185

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SERPINA6	ENST00000341584.4	TSL:1 MANE Select	c.885-1321C>T		intron	N/A	ENSP00000342850.3	P08185
	SERPINA6	ENST00000874318.1		c.1056-1321C>T		intron	N/A	ENSP00000544377.1
	SERPINA6	ENST00000874321.1		c.885-763C>T		intron	N/A	ENSP00000544380.1

Frequencies

GnomAD3 genomes AF: 0.474 AC: 72097 AN: 152020 Hom.: 18270 Cov.: 34

Gnomad AFR AF: 0.375

Gnomad AMI AF: 0.509

Gnomad AMR AF: 0.604

Gnomad ASJ AF: 0.387

Gnomad EAS AF: 0.926

Gnomad SAS AF: 0.650

Gnomad FIN AF: 0.500

Gnomad MID AF: 0.434

Gnomad NFE AF: 0.458

Gnomad OTH AF: 0.476

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

GnomAD4 genome AF: 0.474 AC: 72152 AN: 152138 Hom.: 18291 Cov.: 34 AF XY: 0.487 AC XY: 36223 AN XY: 74380

African (AFR) AF: 0.375 AC: 15562 AN: 41470

American (AMR) AF: 0.605 AC: 9258 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.387 AC: 1344 AN: 3472

East Asian (EAS) AF: 0.927 AC: 4803 AN: 5184

South Asian (SAS) AF: 0.649 AC: 3133 AN: 4826

European-Finnish (FIN) AF: 0.500 AC: 5281 AN: 10564

Middle Eastern (MID) AF: 0.439 AC: 129 AN: 294

European-Non Finnish (NFE) AF: 0.458 AC: 31163 AN: 68006

Other (OTH) AF: 0.480 AC: 1015 AN: 2114

Alfa AF: 0.453 Hom.: 2409

Bravo AF: 0.477

Asia WGS AF: 0.762 AC: 2647 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	0.92
DANN	Benign	0.58
PhyloP100		-2.1
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs8023023; hg19: chr14-94773876;