14-94322780-A-G

Position:

• chr14-94322780-A-G

Variant summary

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

The ENST00000341584.4(SERPINA6):​c.-20+487T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.202 in 152,122 control chromosomes in the GnomAD database, including 3,481 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 0.20 (3481 hom., cov: 33)
• Consequence: SERPINA6 ENST00000341584.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.154

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=-0.82).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.381 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SERPINA6	NM_001756.4	c.-20+487T>C		intron_variant		ENST00000341584.4	NP_001747.3
SERPINA6	XM_047431827.1	c.-20+487T>C		intron_variant			XP_047287783.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SERPINA6	ENST00000341584.4	c.-20+487T>C		intron_variant		1	NM_001756.4	ENSP00000342850	P1
SERPINA6	ENST00000557225.1	c.-188+487T>C		intron_variant		2		ENSP00000452018
SERPINA6	ENST00000555056.1	c.-20+487T>C		intron_variant, NMD_transcript_variant		2		ENSP00000451045

Frequencies

GnomAD3 genomes AF: 0.202 AC: 30707 AN: 152004 Hom.: 3472 Cov.: 33

Gnomad AFR AF: 0.153

Gnomad AMI AF: 0.305

Gnomad AMR AF: 0.150

Gnomad ASJ AF: 0.205

Gnomad EAS AF: 0.395

Gnomad SAS AF: 0.368

Gnomad FIN AF: 0.213

Gnomad MID AF: 0.241

Gnomad NFE AF: 0.213

Gnomad OTH AF: 0.207

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

GnomAD4 genome AF: 0.202 AC: 30735 AN: 152122 Hom.: 3481 Cov.: 33 AF XY: 0.205 AC XY: 15249 AN XY: 74368

Gnomad4 AFR AF: 0.153

Gnomad4 AMR AF: 0.150

Gnomad4 ASJ AF: 0.205

Gnomad4 EAS AF: 0.395

Gnomad4 SAS AF: 0.368

Gnomad4 FIN AF: 0.213

Gnomad4 NFE AF: 0.214

Gnomad4 OTH AF: 0.216

Alfa AF: 0.204 Hom.: 417

Bravo AF: 0.190

Asia WGS AF: 0.356 AC: 1236 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	2.6
DANN	Benign	0.83

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: rs2281518; hg19: chr14-94789117;