14-94310064-T-C

Position:

• chr14-94310064-T-C

Variant summary

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

The NM_001756.4(SERPINA6):​c.614-58A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.741 in 1,580,424 control chromosomes in the GnomAD database, including 437,224 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 0.73 (40627 hom., cov: 32)
  • Exomes 𝑓: 0.74 (396597 hom.)
• Consequence: SERPINA6 NM_001756.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0320

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=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.971 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SERPINA6	NM_001756.4	c.614-58A>G		intron_variant		ENST00000341584.4	NP_001747.3
SERPINA6	XM_047431827.1	c.763-36A>G		intron_variant			XP_047287783.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SERPINA6	ENST00000341584.4	c.614-58A>G		intron_variant		1	NM_001756.4	ENSP00000342850	P1
SERPINA6	ENST00000555056.1	c.763-58A>G		intron_variant, NMD_transcript_variant		2		ENSP00000451045

Frequencies

GnomAD3 genomes AF: 0.726 AC: 110367 AN: 151996 Hom.: 40592 Cov.: 32

Gnomad AFR AF: 0.640

Gnomad AMI AF: 0.779

Gnomad AMR AF: 0.794

Gnomad ASJ AF: 0.597

Gnomad EAS AF: 0.993

Gnomad SAS AF: 0.785

Gnomad FIN AF: 0.778

Gnomad MID AF: 0.674

Gnomad NFE AF: 0.737

Gnomad OTH AF: 0.712

GnomAD4 exome AF: 0.743 AC: 1060902 AN: 1428308 Hom.: 396597 AF XY: 0.744 AC XY: 528752 AN XY: 710474

Gnomad4 AFR exome AF: 0.639

Gnomad4 AMR exome AF: 0.847

Gnomad4 ASJ exome AF: 0.596

Gnomad4 EAS exome AF: 0.996

Gnomad4 SAS exome AF: 0.777

Gnomad4 FIN exome AF: 0.768

Gnomad4 NFE exome AF: 0.733

Gnomad4 OTH exome AF: 0.740

GnomAD4 genome AF: 0.726 AC: 110451 AN: 152116 Hom.: 40627 Cov.: 32 AF XY: 0.731 AC XY: 54383 AN XY: 74354

Gnomad4 AFR AF: 0.640

Gnomad4 AMR AF: 0.794

Gnomad4 ASJ AF: 0.597

Gnomad4 EAS AF: 0.993

Gnomad4 SAS AF: 0.785

Gnomad4 FIN AF: 0.778

Gnomad4 NFE AF: 0.737

Gnomad4 OTH AF: 0.714

Alfa AF: 0.729 Hom.: 8289

Bravo AF: 0.724

Asia WGS AF: 0.875 AC: 3040 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	5.2
DANN	Benign	0.45

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: rs11160168; hg19: chr14-94776401;