rs16910559

chr9-121343931-G-A

Variant summary

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

The NM_004099.6(STOM):c.661-2523C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0588 in 152,182 control chromosomes in the GnomAD database, including 319 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 0.059 (319 hom., cov: 32)
• Consequence: STOM NM_004099.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.16

Genes affected

STOM (HGNC:3383): (stomatin) This gene encodes a member of a highly conserved family of integral membrane proteins. The encoded protein localizes to the cell membrane of red blood cells and other cell types, where it may regulate ion channels and transporters. Loss of localization of the encoded protein is associated with hereditary stomatocytosis, a form of hemolytic anemia. There is a pseudogene for this gene on chromosome 6. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jul 2012]

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 = 0.15 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
STOM	NM_004099.6	c.661-2523C>T		intron_variant		ENST00000286713.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
STOM	ENST00000286713.7	c.661-2523C>T		intron_variant		1	NM_004099.6	P1
STOM	ENST00000347359.3	c.166-2523C>T		intron_variant		2
STOM	ENST00000538954.5	c.487-4290C>T		intron_variant		5

Frequencies

GnomAD3 genomes AF: 0.0588 AC: 8936 AN: 152064 Hom.: 319 Cov.: 32

Gnomad AFR AF: 0.0698

Gnomad AMI AF: 0.0132

Gnomad AMR AF: 0.0498

Gnomad ASJ AF: 0.145

Gnomad EAS AF: 0.159

Gnomad SAS AF: 0.0709

Gnomad FIN AF: 0.0517

Gnomad MID AF: 0.0728

Gnomad NFE AF: 0.0422

Gnomad OTH AF: 0.0779

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

GnomAD4 genome AF: 0.0588 AC: 8943 AN: 152182 Hom.: 319 Cov.: 32 AF XY: 0.0591 AC XY: 4394 AN XY: 74392

Gnomad4 AFR AF: 0.0699

Gnomad4 AMR AF: 0.0497

Gnomad4 ASJ AF: 0.145

Gnomad4 EAS AF: 0.159

Gnomad4 SAS AF: 0.0702

Gnomad4 FIN AF: 0.0517

Gnomad4 NFE AF: 0.0422

Gnomad4 OTH AF: 0.0776

Alfa AF: 0.0505 Hom.: 105

Bravo AF: 0.0584

Asia WGS AF: 0.0970 AC: 338 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
Cadd	Benign	0.22
Dann	Benign	0.49

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: rs16910559; hg19: chr9-124106209;