rs4578059

chr9-17673049-C-T

Variant summary

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

The NM_003026.5(SH3GL2):c.46-74017C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.504 in 151,924 control chromosomes in the GnomAD database, including 20,310 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 0.50 (20310 hom., cov: 32)
• Consequence: SH3GL2 NM_003026.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0570

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.0).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.645 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SH3GL2	NM_003026.5	c.46-74017C>T		intron_variant		ENST00000380607.5
SH3GL2	XM_011518005.4	c.147+54834C>T		intron_variant
SH3GL2	XM_047423730.1	c.-61+65795C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SH3GL2	ENST00000380607.5	c.46-74017C>T		intron_variant		1	NM_003026.5	P1

Frequencies

GnomAD3 genomes AF: 0.503 AC: 76412 AN: 151806 Hom.: 20279 Cov.: 32

Gnomad AFR AF: 0.652

Gnomad AMI AF: 0.360

Gnomad AMR AF: 0.596

Gnomad ASJ AF: 0.349

Gnomad EAS AF: 0.524

Gnomad SAS AF: 0.505

Gnomad FIN AF: 0.484

Gnomad MID AF: 0.439

Gnomad NFE AF: 0.404

Gnomad OTH AF: 0.492

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

GnomAD4 genome AF: 0.504 AC: 76498 AN: 151924 Hom.: 20310 Cov.: 32 AF XY: 0.510 AC XY: 37860 AN XY: 74270

Gnomad4 AFR AF: 0.652

Gnomad4 AMR AF: 0.596

Gnomad4 ASJ AF: 0.349

Gnomad4 EAS AF: 0.524

Gnomad4 SAS AF: 0.506

Gnomad4 FIN AF: 0.484

Gnomad4 NFE AF: 0.404

Gnomad4 OTH AF: 0.490

Alfa AF: 0.477 Hom.: 2267

Bravo AF: 0.520

Asia WGS AF: 0.518 AC: 1801 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
Cadd	Benign	2.2
Dann	Benign	0.43

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: rs4578059; hg19: chr9-17673047; COSMIC: COSV66054911;