14-94475250-G-A

Variant names:

• chr14-94475250-G-A
• rs11626091
• NM_175739.4:c.-18+886C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_175739.4(SERPINA9):​c.-18+886C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.341 in 151,960 control chromosomes in the GnomAD database, including 10,259 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 0.34 (10259 hom., cov: 31)
• Consequence: SERPINA9 NM_175739.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.406
• Publications: 6 publications found

Genes affected

SERPINA9 (HGNC:15995): (serpin family A member 9) Enables serine-type endopeptidase inhibitor activity. Predicted to be involved in negative regulation of endopeptidase activity. Predicted to be located in cytoplasm and membrane. Predicted to be active in extracellular space. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.43 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_175739.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SERPINA9	NM_175739.4	MANE Select	c.-18+886C>T		intron	N/A	NP_783866.3
	SERPINA9	NM_001284275.2		c.-68+886C>T		intron	N/A	NP_001271204.2
	SERPINA9	NM_001042518.2		c.-18+886C>T		intron	N/A	NP_001035983.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SERPINA9	ENST00000674397.2	MANE Select	c.-18+886C>T		intron	N/A	ENSP00000501517.1
	SERPINA9	ENST00000337425.10	TSL:1	c.37+886C>T		intron	N/A	ENSP00000337133.5
	SERPINA9	ENST00000448305.6	TSL:1	c.-68+886C>T		intron	N/A	ENSP00000414092.2

Frequencies

GnomAD3 genomes AF: 0.341 AC: 51819 AN: 151842 Hom.: 10257 Cov.: 31

Gnomad AFR AF: 0.130

Gnomad AMI AF: 0.336

Gnomad AMR AF: 0.437

Gnomad ASJ AF: 0.380

Gnomad EAS AF: 0.280

Gnomad SAS AF: 0.358

Gnomad FIN AF: 0.440

Gnomad MID AF: 0.234

Gnomad NFE AF: 0.434

Gnomad OTH AF: 0.359

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

GnomAD4 genome AF: 0.341 AC: 51830 AN: 151960 Hom.: 10259 Cov.: 31 AF XY: 0.341 AC XY: 25340 AN XY: 74290

African (AFR) AF: 0.130 AC: 5405 AN: 41444

American (AMR) AF: 0.437 AC: 6677 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.380 AC: 1318 AN: 3470

East Asian (EAS) AF: 0.280 AC: 1437 AN: 5128

South Asian (SAS) AF: 0.359 AC: 1729 AN: 4818

European-Finnish (FIN) AF: 0.440 AC: 4650 AN: 10558

Middle Eastern (MID) AF: 0.221 AC: 65 AN: 294

European-Non Finnish (NFE) AF: 0.434 AC: 29494 AN: 67940

Other (OTH) AF: 0.354 AC: 749 AN: 2114

Alfa AF: 0.408 Hom.: 21791

Bravo AF: 0.329

Asia WGS AF: 0.307 AC: 1068 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.37
DANN	Benign	0.53
PhyloP100		-0.41
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs11626091; hg19: chr14-94941587; COSMIC: COSV54078803;