rs1956178

chr14-94320207-C-A

Variant summary

Our verdict is Benign. Variant got -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

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]

ACMG classification

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SERPINA6	NM_001756.4	c.-20+3060G>T		intron_variant		ENST00000341584.4
SERPINA6	XM_047431827.1	c.-20+3060G>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SERPINA6	ENST00000341584.4	c.-20+3060G>T		intron_variant		1	NM_001756.4	P1
SERPINA6	ENST00000557225.1	c.-188+3060G>T		intron_variant		2
SERPINA6	ENST00000555056.1	c.-20+3060G>T		intron_variant, NMD_transcript_variant		2

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

Gnomad4 AFR AF: 0.0392

Gnomad4 AMR AF: 0.265

Gnomad4 ASJ AF: 0.118

Gnomad4 EAS AF: 0.463

Gnomad4 SAS AF: 0.132

Gnomad4 FIN AF: 0.214

Gnomad4 NFE AF: 0.186

Gnomad4 OTH AF: 0.177

Alfa AF: 0.175 Hom.: 382

Bravo AF: 0.168

Asia WGS AF: 0.278 AC: 962 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
Cadd	Benign	2.6
Dann	Benign	0.64

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

Publications

LitVar

Other links and lift over

dbSNP: rs1956178; hg19: chr14-94786544;