14-94306784-A-G

Variant names:

• chr14-94306784-A-G
• rs3790036
• NM_001756.4:c.885-566T>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.885-566T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.154 in 152,282 control chromosomes in the GnomAD database, including 2,524 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 0.15 (2524 hom., cov: 33)
• Consequence: SERPINA6 NM_001756.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.42
• Publications: 6 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=-1.05).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.465 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SERPINA6	NM_001756.4	c.885-566T>C		intron_variant	Intron 3 of 4	ENST00000341584.4	NP_001747.3
SERPINA6	XM_047431827.1	c.1056-566T>C		intron_variant	Intron 3 of 4		XP_047287783.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SERPINA6	ENST00000341584.4	c.885-566T>C		intron_variant	Intron 3 of 4	1	NM_001756.4	ENSP00000342850.3
SERPINA6	ENST00000555056.1	n.*197-566T>C		intron_variant	Intron 3 of 4	2		ENSP00000451045.1

Frequencies

GnomAD3 genomes AF: 0.154 AC: 23432 AN: 152164 Hom.: 2524 Cov.: 33

Gnomad AFR AF: 0.0387

Gnomad AMI AF: 0.127

Gnomad AMR AF: 0.233

Gnomad ASJ AF: 0.132

Gnomad EAS AF: 0.481

Gnomad SAS AF: 0.134

Gnomad FIN AF: 0.216

Gnomad MID AF: 0.0823

Gnomad NFE AF: 0.175

Gnomad OTH AF: 0.153

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

GnomAD4 genome AF: 0.154 AC: 23430 AN: 152282 Hom.: 2524 Cov.: 33 AF XY: 0.159 AC XY: 11822 AN XY: 74446

African (AFR) AF: 0.0386 AC: 1605 AN: 41578

American (AMR) AF: 0.233 AC: 3571 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.132 AC: 458 AN: 3470

East Asian (EAS) AF: 0.481 AC: 2487 AN: 5172

South Asian (SAS) AF: 0.134 AC: 647 AN: 4832

European-Finnish (FIN) AF: 0.216 AC: 2285 AN: 10600

Middle Eastern (MID) AF: 0.0884 AC: 26 AN: 294

European-Non Finnish (NFE) AF: 0.175 AC: 11916 AN: 68016

Other (OTH) AF: 0.151 AC: 319 AN: 2114

Alfa AF: 0.167 Hom.: 4411

Bravo AF: 0.159

Asia WGS AF: 0.278 AC: 966 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.1
CADD	Benign	0.14
DANN	Benign	0.26
PhyloP100		-2.4
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: rs3790036; hg19: chr14-94773121;