14-94307074-C-T

Position:

• chr14-94307074-C-T

Variant summary

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

The NM_001756.4(SERPINA6):​c.885-856G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.742 in 152,044 control chromosomes in the GnomAD database, including 42,495 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 0.74 (42495 hom., cov: 31)
• Consequence: SERPINA6 NM_001756.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.677

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=-1.01).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.973 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SERPINA6	NM_001756.4	c.885-856G>A		intron_variant		ENST00000341584.4
SERPINA6	XM_047431827.1	c.1056-856G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SERPINA6	ENST00000341584.4	c.885-856G>A		intron_variant		1	NM_001756.4	P1
SERPINA6	ENST00000555056.1	c.*197-856G>A		intron_variant, NMD_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.742 AC: 112678 AN: 151924 Hom.: 42462 Cov.: 31

Gnomad AFR AF: 0.842

Gnomad AMI AF: 0.686

Gnomad AMR AF: 0.640

Gnomad ASJ AF: 0.648

Gnomad EAS AF: 0.996

Gnomad SAS AF: 0.732

Gnomad FIN AF: 0.736

Gnomad MID AF: 0.728

Gnomad NFE AF: 0.692

Gnomad OTH AF: 0.728

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

GnomAD4 genome AF: 0.742 AC: 112762 AN: 152044 Hom.: 42495 Cov.: 31 AF XY: 0.740 AC XY: 54976 AN XY: 74304

Gnomad4 AFR AF: 0.842

Gnomad4 AMR AF: 0.639

Gnomad4 ASJ AF: 0.648

Gnomad4 EAS AF: 0.996

Gnomad4 SAS AF: 0.732

Gnomad4 FIN AF: 0.736

Gnomad4 NFE AF: 0.692

Gnomad4 OTH AF: 0.731

Alfa AF: 0.703 Hom.: 14555

Bravo AF: 0.743

Asia WGS AF: 0.863 AC: 3001 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.15
DANN	Benign	0.46

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs2144835; hg19: chr14-94773411;