rs3808772

Positions:

• chr9-17598289-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+19002C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.722 in 152,104 control chromosomes in the GnomAD database, including 39,917 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 0.72 (39917 hom., cov: 32)
• Consequence: SH3GL2 NM_003026.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.352

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=-0.86).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.768 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SH3GL2	NM_003026.5	c.45+19002C>T		intron_variant		ENST00000380607.5	NP_003017.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SH3GL2	ENST00000380607.5	c.45+19002C>T		intron_variant		1	NM_003026.5	ENSP00000369981	P1
SH3GL2	ENST00000467085.1	n.206+19002C>T		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.722 AC: 109766 AN: 151986 Hom.: 39882 Cov.: 32

Gnomad AFR AF: 0.776

Gnomad AMI AF: 0.731

Gnomad AMR AF: 0.738

Gnomad ASJ AF: 0.715

Gnomad EAS AF: 0.530

Gnomad SAS AF: 0.589

Gnomad FIN AF: 0.714

Gnomad MID AF: 0.696

Gnomad NFE AF: 0.712

Gnomad OTH AF: 0.736

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

GnomAD4 genome AF: 0.722 AC: 109860 AN: 152104 Hom.: 39917 Cov.: 32 AF XY: 0.719 AC XY: 53451 AN XY: 74362

Gnomad4 AFR AF: 0.775

Gnomad4 AMR AF: 0.737

Gnomad4 ASJ AF: 0.715

Gnomad4 EAS AF: 0.530

Gnomad4 SAS AF: 0.590

Gnomad4 FIN AF: 0.714

Gnomad4 NFE AF: 0.711

Gnomad4 OTH AF: 0.736

Alfa AF: 0.711 Hom.: 79947

Bravo AF: 0.726

Asia WGS AF: 0.603 AC: 2095 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	1.6
DANN	Benign	0.29

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: rs3808772; hg19: chr9-17598287;