rs306796

Positions:

• chr9-121365057-C-T

Variant summary

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

The NM_004099.6(STOM):​c.61+5070G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.327 in 151,672 control chromosomes in the GnomAD database, including 8,378 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 0.33 (8378 hom., cov: 31)
• Consequence: STOM NM_004099.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.984

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=-0.88).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.391 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
STOM	NM_004099.6	c.61+5070G>A		intron_variant		ENST00000286713.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
STOM	ENST00000286713.7	c.61+5070G>A		intron_variant		1	NM_004099.6	P1
STOM	ENST00000347359.3	c.61+5070G>A		intron_variant		2
STOM	ENST00000538954.5	c.61+5070G>A		intron_variant		5

Frequencies

GnomAD3 genomes AF: 0.327 AC: 49570 AN: 151552 Hom.: 8372 Cov.: 31

Gnomad AFR AF: 0.316

Gnomad AMI AF: 0.466

Gnomad AMR AF: 0.400

Gnomad ASJ AF: 0.394

Gnomad EAS AF: 0.158

Gnomad SAS AF: 0.251

Gnomad FIN AF: 0.252

Gnomad MID AF: 0.386

Gnomad NFE AF: 0.341

Gnomad OTH AF: 0.332

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

GnomAD4 genome AF: 0.327 AC: 49612 AN: 151672 Hom.: 8378 Cov.: 31 AF XY: 0.323 AC XY: 23901 AN XY: 74106

Gnomad4 AFR AF: 0.316

Gnomad4 AMR AF: 0.400

Gnomad4 ASJ AF: 0.394

Gnomad4 EAS AF: 0.158

Gnomad4 SAS AF: 0.253

Gnomad4 FIN AF: 0.252

Gnomad4 NFE AF: 0.341

Gnomad4 OTH AF: 0.332

Alfa AF: 0.349 Hom.: 9136

Bravo AF: 0.342

Asia WGS AF: 0.233 AC: 809 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.036
DANN	Benign	0.62

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: rs306796; hg19: chr9-124127335;