rs3808747

chr9-17626618-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.45+47331C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.165 in 152,104 control chromosomes in the GnomAD database, including 2,169 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 0.17 (2169 hom., cov: 32)
• Consequence: SH3GL2 NM_003026.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0320

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=-0.84).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.206 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SH3GL2	NM_003026.5	c.45+47331C>T		intron_variant		ENST00000380607.5
SH3GL2	XM_011518005.4	c.147+8403C>T		intron_variant
SH3GL2	XM_047423730.1	c.-61+19364C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SH3GL2	ENST00000380607.5	c.45+47331C>T		intron_variant		1	NM_003026.5	P1
SH3GL2	ENST00000467085.1	n.207-3736C>T		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.165 AC: 25122 AN: 151984 Hom.: 2166 Cov.: 32

Gnomad AFR AF: 0.209

Gnomad AMI AF: 0.149

Gnomad AMR AF: 0.137

Gnomad ASJ AF: 0.202

Gnomad EAS AF: 0.140

Gnomad SAS AF: 0.171

Gnomad FIN AF: 0.139

Gnomad MID AF: 0.232

Gnomad NFE AF: 0.148

Gnomad OTH AF: 0.160

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

GnomAD4 genome AF: 0.165 AC: 25141 AN: 152104 Hom.: 2169 Cov.: 32 AF XY: 0.165 AC XY: 12285 AN XY: 74342

Gnomad4 AFR AF: 0.210

Gnomad4 AMR AF: 0.137

Gnomad4 ASJ AF: 0.202

Gnomad4 EAS AF: 0.141

Gnomad4 SAS AF: 0.170

Gnomad4 FIN AF: 0.139

Gnomad4 NFE AF: 0.148

Gnomad4 OTH AF: 0.158

Alfa AF: 0.155 Hom.: 4129

Bravo AF: 0.166

Asia WGS AF: 0.135 AC: 467 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
Cadd	Benign	1.7
Dann	Benign	0.78

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: rs3808747; hg19: chr9-17626616;