rs1052886

Positions:

• chr6-2889956-A-G

Variant summary

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

The NM_004155.6(SERPINB9):​c.*207T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.198 in 468,126 control chromosomes in the GnomAD database, including 10,439 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 0.18 (2969 hom., cov: 31)
  • Exomes 𝑓: 0.21 (7470 hom.)
• Consequence: SERPINB9 NM_004155.6 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.736

Genes affected

SERPINB9 (HGNC:8955): (serpin family B member 9) This gene encodes a member of the serine protease inhibitor family which are also known as serpins. The encoded protein belongs to a subfamily of intracellular serpins. This protein inhibits the activity of the effector molecule granzyme B. Overexpression of this protein may prevent cytotoxic T-lymphocytes from eliminating certain tumor cells. A pseudogene of this gene is found on chromosome 6. [provided by RefSeq, Mar 2012]

SERPINB9-AS1 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.225 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SERPINB9	NM_004155.6	c.*207T>C		3_prime_UTR_variant	7/7	ENST00000380698.5
SERPINB9-AS1	NR_110841.1	n.224+5116A>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SERPINB9	ENST00000380698.5	c.*207T>C		3_prime_UTR_variant	7/7	1	NM_004155.6	P1

Frequencies

GnomAD3 genomes AF: 0.182 AC: 27658 AN: 151940 Hom.: 2967 Cov.: 31

Gnomad AFR AF: 0.0943

Gnomad AMI AF: 0.252

Gnomad AMR AF: 0.137

Gnomad ASJ AF: 0.153

Gnomad EAS AF: 0.129

Gnomad SAS AF: 0.115

Gnomad FIN AF: 0.357

Gnomad MID AF: 0.158

Gnomad NFE AF: 0.228

Gnomad OTH AF: 0.174

GnomAD4 exome AF: 0.206 AC: 65063 AN: 316068 Hom.: 7470 Cov.: 4 AF XY: 0.205 AC XY: 33199 AN XY: 162160

Gnomad4 AFR exome AF: 0.0960

Gnomad4 AMR exome AF: 0.113

Gnomad4 ASJ exome AF: 0.139

Gnomad4 EAS exome AF: 0.146

Gnomad4 SAS exome AF: 0.107

Gnomad4 FIN exome AF: 0.348

Gnomad4 NFE exome AF: 0.224

Gnomad4 OTH exome AF: 0.192

GnomAD4 genome AF: 0.182 AC: 27662 AN: 152058 Hom.: 2969 Cov.: 31 AF XY: 0.184 AC XY: 13646 AN XY: 74316

Gnomad4 AFR AF: 0.0940

Gnomad4 AMR AF: 0.137

Gnomad4 ASJ AF: 0.153

Gnomad4 EAS AF: 0.129

Gnomad4 SAS AF: 0.115

Gnomad4 FIN AF: 0.357

Gnomad4 NFE AF: 0.228

Gnomad4 OTH AF: 0.176

Alfa AF: 0.211 Hom.: 5393

Bravo AF: 0.162

Asia WGS AF: 0.149 AC: 517 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	1.0
DANN	Benign	0.70
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0

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: rs1052886; hg19: chr6-2890190;