14-94307113-C-T

Variant names:

• chr14-94307113-C-T
• rs11629171
• NM_001756.4:c.885-895G>A

Variant summary

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

The NM_001756.4(SERPINA6):​c.885-895G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.303 in 152,040 control chromosomes in the GnomAD database, including 8,194 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 0.30 (8194 hom., cov: 32)
• Consequence: SERPINA6 NM_001756.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.879
• Publications: 10 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=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.867 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.885-895G>A		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.885-895G>A		intron	N/A	ENSP00000342850.3
	SERPINA6	ENST00000555056.1	TSL:2	n.*197-895G>A		intron	N/A	ENSP00000451045.1

Frequencies

GnomAD3 genomes AF: 0.303 AC: 46103 AN: 151922 Hom.: 8191 Cov.: 32

Gnomad AFR AF: 0.244

Gnomad AMI AF: 0.330

Gnomad AMR AF: 0.321

Gnomad ASJ AF: 0.240

Gnomad EAS AF: 0.888

Gnomad SAS AF: 0.452

Gnomad FIN AF: 0.350

Gnomad MID AF: 0.272

Gnomad NFE AF: 0.277

Gnomad OTH AF: 0.299

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

GnomAD4 genome AF: 0.303 AC: 46119 AN: 152040 Hom.: 8194 Cov.: 32 AF XY: 0.313 AC XY: 23275 AN XY: 74292

African (AFR) AF: 0.243 AC: 10087 AN: 41446

American (AMR) AF: 0.321 AC: 4901 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.240 AC: 832 AN: 3468

East Asian (EAS) AF: 0.888 AC: 4596 AN: 5174

South Asian (SAS) AF: 0.451 AC: 2173 AN: 4822

European-Finnish (FIN) AF: 0.350 AC: 3697 AN: 10554

Middle Eastern (MID) AF: 0.269 AC: 79 AN: 294

European-Non Finnish (NFE) AF: 0.277 AC: 18809 AN: 67978

Other (OTH) AF: 0.306 AC: 645 AN: 2110

Alfa AF: 0.287 Hom.: 29407

Bravo AF: 0.302

Asia WGS AF: 0.633 AC: 2196 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.36
DANN	Benign	0.58
PhyloP100		-0.88
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: rs11629171; hg19: chr14-94773450;