rs11160169

Positions:

• chr14-94310104-C-A
• chr14-94310104-C-G

Variant summary

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

The NM_001756.4(SERPINA6):​c.614-98G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.485 in 1,242,462 control chromosomes in the GnomAD database, including 154,171 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 0.47 (18168 hom., cov: 32)
  • Exomes 𝑓: 0.49 (136003 hom.)
• Consequence: SERPINA6 NM_001756.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.09

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 (EAS) allele frequency at 95% confidence interval = 0.905 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SERPINA6	NM_001756.4	c.614-98G>T		intron_variant		ENST00000341584.4	NP_001747.3
SERPINA6	XM_047431827.1	c.763-76G>T		intron_variant			XP_047287783.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SERPINA6	ENST00000341584.4	c.614-98G>T		intron_variant		1	NM_001756.4	ENSP00000342850.3
SERPINA6	ENST00000555056.1	n.763-98G>T		intron_variant		2		ENSP00000451045.1

Frequencies

GnomAD3 genomes AF: 0.472 AC: 71718 AN: 151864 Hom.: 18147 Cov.: 32

Gnomad AFR AF: 0.367

Gnomad AMI AF: 0.511

Gnomad AMR AF: 0.604

Gnomad ASJ AF: 0.387

Gnomad EAS AF: 0.927

Gnomad SAS AF: 0.649

Gnomad FIN AF: 0.500

Gnomad MID AF: 0.434

Gnomad NFE AF: 0.459

Gnomad OTH AF: 0.480

GnomAD4 exome AF: 0.486 AC: 530469 AN: 1090480 Hom.: 136003 AF XY: 0.492 AC XY: 272454 AN XY: 553420

Gnomad4 AFR exome AF: 0.357

Gnomad4 AMR exome AF: 0.686

Gnomad4 ASJ exome AF: 0.390

Gnomad4 EAS exome AF: 0.901

Gnomad4 SAS exome AF: 0.624

Gnomad4 FIN exome AF: 0.483

Gnomad4 NFE exome AF: 0.453

Gnomad4 OTH exome AF: 0.494

GnomAD4 genome AF: 0.472 AC: 71773 AN: 151982 Hom.: 18168 Cov.: 32 AF XY: 0.485 AC XY: 36041 AN XY: 74276

Gnomad4 AFR AF: 0.367

Gnomad4 AMR AF: 0.605

Gnomad4 ASJ AF: 0.387

Gnomad4 EAS AF: 0.927

Gnomad4 SAS AF: 0.649

Gnomad4 FIN AF: 0.500

Gnomad4 NFE AF: 0.459

Gnomad4 OTH AF: 0.484

Alfa AF: 0.466 Hom.: 28743

Bravo AF: 0.475

Asia WGS AF: 0.762 AC: 2646 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	0.14
DANN	Benign	0.40

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: rs11160169; hg19: chr14-94776441;