rs1536076

Variant names:

• chr9-17731923-T-G
• rs1536076
• NM_003026.5:c.46-15143T>G

Variant summary

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

The NM_003026.5(SH3GL2):​c.46-15143T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.198 in 152,084 control chromosomes in the GnomAD database, including 3,668 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 0.20 (3668 hom., cov: 33)
• Consequence: SH3GL2 NM_003026.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.139
• Publications: 9 publications found

Genes affected

SH3GL2 (HGNC:10831): (SH3 domain containing GRB2 like 2, endophilin A1) Enables identical protein binding activity. Involved in negative regulation of blood-brain barrier permeability; negative regulation of gene expression; and negative regulation of protein phosphorylation. Located in perinuclear region of cytoplasm. [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=-0.87).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.37 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003026.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SH3GL2	NM_003026.5	MANE Select	c.46-15143T>G		intron	N/A	NP_003017.1	Q99962

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SH3GL2	ENST00000380607.5	TSL:1 MANE Select	c.46-15143T>G		intron	N/A	ENSP00000369981.4	Q99962
	SH3GL2	ENST00000955338.1		c.112-15143T>G		intron	N/A	ENSP00000625397.1
	SH3GL2	ENST00000917907.1		c.46-29514T>G		intron	N/A	ENSP00000587966.1

Frequencies

GnomAD3 genomes AF: 0.198 AC: 30096 AN: 151966 Hom.: 3671 Cov.: 33

Gnomad AFR AF: 0.0557

Gnomad AMI AF: 0.275

Gnomad AMR AF: 0.226

Gnomad ASJ AF: 0.217

Gnomad EAS AF: 0.384

Gnomad SAS AF: 0.339

Gnomad FIN AF: 0.285

Gnomad MID AF: 0.234

Gnomad NFE AF: 0.238

Gnomad OTH AF: 0.221

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

GnomAD4 genome AF: 0.198 AC: 30092 AN: 152084 Hom.: 3668 Cov.: 33 AF XY: 0.204 AC XY: 15181 AN XY: 74322

African (AFR) AF: 0.0557 AC: 2315 AN: 41542

American (AMR) AF: 0.226 AC: 3443 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.217 AC: 752 AN: 3472

East Asian (EAS) AF: 0.384 AC: 1969 AN: 5126

South Asian (SAS) AF: 0.338 AC: 1632 AN: 4822

European-Finnish (FIN) AF: 0.285 AC: 3016 AN: 10588

Middle Eastern (MID) AF: 0.235 AC: 69 AN: 294

European-Non Finnish (NFE) AF: 0.238 AC: 16180 AN: 67962

Other (OTH) AF: 0.221 AC: 466 AN: 2108

Alfa AF: 0.234 Hom.: 3820

Bravo AF: 0.189

Asia WGS AF: 0.326 AC: 1132 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	1.3
DANN	Benign	0.67
PhyloP100		-0.14
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: rs1536076; hg19: chr9-17731921; COSMIC: COSV66055261;