14-94308658-A-G

Variant names:

• chr14-94308658-A-G
• rs11622665
• NM_001756.4:c.884+1078T>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.884+1078T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.143 in 152,194 control chromosomes in the GnomAD database, including 2,116 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 (2116 hom., cov: 32)
• Consequence: SERPINA6 NM_001756.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.976
• 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=-0.89).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.27 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SERPINA6	NM_001756.4	c.884+1078T>C		intron_variant	Intron 3 of 4	ENST00000341584.4	NP_001747.3
SERPINA6	XM_047431827.1	c.1055+1078T>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.884+1078T>C		intron_variant	Intron 3 of 4	1	NM_001756.4	ENSP00000342850.3
SERPINA6	ENST00000555056.1	n.*196+1078T>C		intron_variant	Intron 3 of 4	2		ENSP00000451045.1

Frequencies

GnomAD3 genomes AF: 0.143 AC: 21742 AN: 152076 Hom.: 2110 Cov.: 32

Gnomad AFR AF: 0.0462

Gnomad AMI AF: 0.176

Gnomad AMR AF: 0.276

Gnomad ASJ AF: 0.146

Gnomad EAS AF: 0.00250

Gnomad SAS AF: 0.141

Gnomad FIN AF: 0.149

Gnomad MID AF: 0.131

Gnomad NFE AF: 0.181

Gnomad OTH AF: 0.162

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

GnomAD4 genome AF: 0.143 AC: 21762 AN: 152194 Hom.: 2116 Cov.: 32 AF XY: 0.146 AC XY: 10852 AN XY: 74412

African (AFR) AF: 0.0462 AC: 1918 AN: 41536

American (AMR) AF: 0.277 AC: 4229 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.146 AC: 506 AN: 3466

East Asian (EAS) AF: 0.00251 AC: 13 AN: 5182

South Asian (SAS) AF: 0.142 AC: 684 AN: 4822

European-Finnish (FIN) AF: 0.149 AC: 1583 AN: 10598

Middle Eastern (MID) AF: 0.137 AC: 40 AN: 292

European-Non Finnish (NFE) AF: 0.181 AC: 12292 AN: 67996

Other (OTH) AF: 0.159 AC: 337 AN: 2114

Alfa AF: 0.156 Hom.: 1017

Bravo AF: 0.146

Asia WGS AF: 0.0780 AC: 270 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.14
DANN	Benign	0.83
PhyloP100		-0.98
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: rs11622665; hg19: chr14-94774995;