14-94305204-C-T

Variant names:

• chr14-94305204-C-T
• rs941601
• NM_001756.4:c.1033-601G>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.1033-601G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.185 in 152,006 control chromosomes in the GnomAD database, including 3,367 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 0.18 (3367 hom., cov: 32)
• Consequence: SERPINA6 NM_001756.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.799
• Publications: 8 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=-0.96).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.334 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SERPINA6	NM_001756.4	c.1033-601G>A		intron_variant	Intron 4 of 4	ENST00000341584.4	NP_001747.3
SERPINA6	XM_047431827.1	c.1204-601G>A		intron_variant	Intron 4 of 4		XP_047287783.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SERPINA6	ENST00000341584.4	c.1033-601G>A		intron_variant	Intron 4 of 4	1	NM_001756.4	ENSP00000342850.3
SERPINA6	ENST00000555056.1	n.*345-601G>A		intron_variant	Intron 4 of 4	2		ENSP00000451045.1

Frequencies

GnomAD3 genomes AF: 0.184 AC: 28011 AN: 151888 Hom.: 3352 Cov.: 32

Gnomad AFR AF: 0.338

Gnomad AMI AF: 0.0844

Gnomad AMR AF: 0.130

Gnomad ASJ AF: 0.199

Gnomad EAS AF: 0.00482

Gnomad SAS AF: 0.0892

Gnomad FIN AF: 0.108

Gnomad MID AF: 0.212

Gnomad NFE AF: 0.136

Gnomad OTH AF: 0.193

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

GnomAD4 genome AF: 0.185 AC: 28060 AN: 152006 Hom.: 3367 Cov.: 32 AF XY: 0.179 AC XY: 13295 AN XY: 74310

African (AFR) AF: 0.338 AC: 14015 AN: 41422

American (AMR) AF: 0.130 AC: 1986 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.199 AC: 691 AN: 3470

East Asian (EAS) AF: 0.00484 AC: 25 AN: 5170

South Asian (SAS) AF: 0.0891 AC: 429 AN: 4814

European-Finnish (FIN) AF: 0.108 AC: 1136 AN: 10562

Middle Eastern (MID) AF: 0.214 AC: 63 AN: 294

European-Non Finnish (NFE) AF: 0.136 AC: 9235 AN: 67976

Other (OTH) AF: 0.191 AC: 403 AN: 2112

Alfa AF: 0.155 Hom.: 6417

Bravo AF: 0.193

Asia WGS AF: 0.0760 AC: 264 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	0.69
DANN	Benign	0.30
PhyloP100		-0.80
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: rs941601; hg19: chr14-94771541;