rs1956178

Variant names:

• chr14-94320207-C-A
• rs1956178
• NM_001756.4:c.-20+3060G>T

Variant summary

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

The NM_001756.4(SERPINA6):​c.-20+3060G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.162 in 152,072 control chromosomes in the GnomAD database, including 2,748 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 0.16 (2748 hom., cov: 32)
• Consequence: SERPINA6 NM_001756.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.194
• Publications: 4 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: AR, AD, SD, Unknown Classification: STRONG, MODERATE, SUPPORTIVE, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics, PanelApp Australia, Orphanet

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 = 0.447 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SERPINA6	NM_001756.4	MANE Select	c.-20+3060G>T		intron	N/A	NP_001747.3	P08185

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SERPINA6	ENST00000341584.4	TSL:1 MANE Select	c.-20+3060G>T		intron	N/A	ENSP00000342850.3	P08185
	SERPINA6	ENST00000874318.1		c.-20+3060G>T		intron	N/A	ENSP00000544377.1
	SERPINA6	ENST00000874321.1		c.-20+3060G>T		intron	N/A	ENSP00000544380.1

Frequencies

GnomAD3 genomes AF: 0.162 AC: 24568 AN: 151954 Hom.: 2746 Cov.: 32

Gnomad AFR AF: 0.0393

Gnomad AMI AF: 0.152

Gnomad AMR AF: 0.265

Gnomad ASJ AF: 0.118

Gnomad EAS AF: 0.462

Gnomad SAS AF: 0.132

Gnomad FIN AF: 0.214

Gnomad MID AF: 0.127

Gnomad NFE AF: 0.186

Gnomad OTH AF: 0.179

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

GnomAD4 genome AF: 0.162 AC: 24566 AN: 152072 Hom.: 2748 Cov.: 32 AF XY: 0.167 AC XY: 12411 AN XY: 74334

African (AFR) AF: 0.0392 AC: 1628 AN: 41506

American (AMR) AF: 0.265 AC: 4048 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.118 AC: 408 AN: 3472

East Asian (EAS) AF: 0.463 AC: 2383 AN: 5152

South Asian (SAS) AF: 0.132 AC: 636 AN: 4816

European-Finnish (FIN) AF: 0.214 AC: 2261 AN: 10562

Middle Eastern (MID) AF: 0.127 AC: 37 AN: 292

European-Non Finnish (NFE) AF: 0.186 AC: 12654 AN: 67990

Other (OTH) AF: 0.177 AC: 373 AN: 2112

Alfa AF: 0.123 Hom.: 416

Bravo AF: 0.168

Asia WGS AF: 0.278 AC: 962 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	2.6
DANN	Benign	0.64
PhyloP100		0.19
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: rs1956178; hg19: chr14-94786544;