rs8022616

Variant names:

• chr14-94307608-A-G
• rs8022616
• NM_001756.4:c.885-1390T>C

Variant summary

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

The NM_001756.4(SERPINA6):​c.885-1390T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.138 in 152,228 control chromosomes in the GnomAD database, including 1,855 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 0.14 (1855 hom., cov: 34)
• Consequence: SERPINA6 NM_001756.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.02
• Publications: 9 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: SD, Unknown, AD, AR Classification: STRONG, MODERATE, SUPPORTIVE, LIMITED Submitted by: Orphanet, Labcorp Genetics (formerly Invitae), Ambry Genetics

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.395 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SERPINA6	NM_001756.4	MANE Select	c.885-1390T>C		intron	N/A	NP_001747.3

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SERPINA6	ENST00000341584.4	TSL:1 MANE Select	c.885-1390T>C		intron	N/A	ENSP00000342850.3
	SERPINA6	ENST00000555056.1	TSL:2	n.*197-1390T>C		intron	N/A	ENSP00000451045.1

Frequencies

GnomAD3 genomes AF: 0.138 AC: 21038 AN: 152110 Hom.: 1848 Cov.: 34

Gnomad AFR AF: 0.167

Gnomad AMI AF: 0.206

Gnomad AMR AF: 0.0804

Gnomad ASJ AF: 0.107

Gnomad EAS AF: 0.409

Gnomad SAS AF: 0.318

Gnomad FIN AF: 0.133

Gnomad MID AF: 0.190

Gnomad NFE AF: 0.102

Gnomad OTH AF: 0.137

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

GnomAD4 genome AF: 0.138 AC: 21056 AN: 152228 Hom.: 1855 Cov.: 34 AF XY: 0.143 AC XY: 10671 AN XY: 74414

African (AFR) AF: 0.167 AC: 6920 AN: 41526

American (AMR) AF: 0.0802 AC: 1227 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.107 AC: 372 AN: 3470

East Asian (EAS) AF: 0.409 AC: 2116 AN: 5172

South Asian (SAS) AF: 0.318 AC: 1533 AN: 4822

European-Finnish (FIN) AF: 0.133 AC: 1407 AN: 10586

Middle Eastern (MID) AF: 0.180 AC: 53 AN: 294

European-Non Finnish (NFE) AF: 0.102 AC: 6930 AN: 68032

Other (OTH) AF: 0.147 AC: 310 AN: 2114

Alfa AF: 0.123 Hom.: 1289

Bravo AF: 0.131

Asia WGS AF: 0.354 AC: 1229 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	0.11
DANN	Benign	0.30
PhyloP100		-2.0
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: rs8022616; hg19: chr14-94773945; COSMIC: COSV58583842;