rs2144834

Positions:

• chr14-94307297-G-A
• chr14-94307297-G-C

Variant summary

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

The NM_001756.4(SERPINA6):​c.885-1079C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.206 in 151,950 control chromosomes in the GnomAD database, including 3,403 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 0.21 (3403 hom., cov: 32)
• Consequence: SERPINA6 NM_001756.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.219

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=-0.91).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.245 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SERPINA6	NM_001756.4	c.885-1079C>T		intron_variant		ENST00000341584.4	NP_001747.3
SERPINA6	XM_047431827.1	c.1056-1079C>T		intron_variant			XP_047287783.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SERPINA6	ENST00000341584.4	c.885-1079C>T		intron_variant		1	NM_001756.4	ENSP00000342850	P1
SERPINA6	ENST00000555056.1	c.*197-1079C>T		intron_variant, NMD_transcript_variant		2		ENSP00000451045

Frequencies

GnomAD3 genomes AF: 0.206 AC: 31306 AN: 151832 Hom.: 3399 Cov.: 32

Gnomad AFR AF: 0.174

Gnomad AMI AF: 0.252

Gnomad AMR AF: 0.157

Gnomad ASJ AF: 0.195

Gnomad EAS AF: 0.0660

Gnomad SAS AF: 0.131

Gnomad FIN AF: 0.242

Gnomad MID AF: 0.193

Gnomad NFE AF: 0.248

Gnomad OTH AF: 0.187

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

GnomAD4 genome AF: 0.206 AC: 31312 AN: 151950 Hom.: 3403 Cov.: 32 AF XY: 0.200 AC XY: 14862 AN XY: 74256

Gnomad4 AFR AF: 0.174

Gnomad4 AMR AF: 0.156

Gnomad4 ASJ AF: 0.195

Gnomad4 EAS AF: 0.0660

Gnomad4 SAS AF: 0.131

Gnomad4 FIN AF: 0.242

Gnomad4 NFE AF: 0.248

Gnomad4 OTH AF: 0.186

Alfa AF: 0.231 Hom.: 8617

Bravo AF: 0.198

Asia WGS AF: 0.100 AC: 349 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	3.4
DANN	Benign	0.72

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: rs2144834; hg19: chr14-94773634;