rs8022616

Positions:

• chr14-94307608-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001756.4(SERPINA6):​c.885-1390T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.138 in 152,228 control chromosomes in the GnomAD database, including 1,855 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 (1855 hom., cov: 34)
• Consequence: SERPINA6 NM_001756.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.02

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 = 0.395 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SERPINA6	NM_001756.4	c.885-1390T>C		intron_variant		ENST00000341584.4
SERPINA6	XM_047431827.1	c.1056-1390T>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SERPINA6	ENST00000341584.4	c.885-1390T>C		intron_variant		1	NM_001756.4	P1
SERPINA6	ENST00000555056.1	c.*197-1390T>C		intron_variant, NMD_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.138 AC: 21038 AN: 152110 Hom.: 1848 Cov.: 34

Gnomad AFR AF: 0.167

Gnomad AMI AF: 0.206

Gnomad AMR AF: 0.0804

Gnomad ASJ AF: 0.107

Gnomad EAS AF: 0.409

Gnomad SAS AF: 0.318

Gnomad FIN AF: 0.133

Gnomad MID AF: 0.190

Gnomad NFE AF: 0.102

Gnomad OTH AF: 0.137

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

GnomAD4 genome AF: 0.138 AC: 21056 AN: 152228 Hom.: 1855 Cov.: 34 AF XY: 0.143 AC XY: 10671 AN XY: 74414

Gnomad4 AFR AF: 0.167

Gnomad4 AMR AF: 0.0802

Gnomad4 ASJ AF: 0.107

Gnomad4 EAS AF: 0.409

Gnomad4 SAS AF: 0.318

Gnomad4 FIN AF: 0.133

Gnomad4 NFE AF: 0.102

Gnomad4 OTH AF: 0.147

Alfa AF: 0.119 Hom.: 727

Bravo AF: 0.131

Asia WGS AF: 0.354 AC: 1229 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	0.11
DANN	Benign	0.30

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: rs8022616; hg19: chr14-94773945; COSMIC: COSV58583842;