9-17613442-A-G

Position:

• chr9-17613442-A-G

Variant summary

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

The NM_003026.5(SH3GL2):​c.45+34155A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.845 in 152,122 control chromosomes in the GnomAD database, including 57,091 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 0.85 (57091 hom., cov: 31)
• Consequence: SH3GL2 NM_003026.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.61

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=-0.68).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.968 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SH3GL2	NM_003026.5	c.45+34155A>G		intron_variant		ENST00000380607.5
SH3GL2	XM_047423730.1	c.-61+6188A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SH3GL2	ENST00000380607.5	c.45+34155A>G		intron_variant		1	NM_003026.5	P1
SH3GL2	ENST00000467085.1	n.207-16912A>G		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.846 AC: 128538 AN: 152004 Hom.: 57082 Cov.: 31

Gnomad AFR AF: 0.541

Gnomad AMI AF: 0.996

Gnomad AMR AF: 0.925

Gnomad ASJ AF: 0.986

Gnomad EAS AF: 0.890

Gnomad SAS AF: 0.991

Gnomad FIN AF: 0.978

Gnomad MID AF: 0.962

Gnomad NFE AF: 0.968

Gnomad OTH AF: 0.891

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

GnomAD4 genome AF: 0.845 AC: 128584 AN: 152122 Hom.: 57091 Cov.: 31 AF XY: 0.852 AC XY: 63358 AN XY: 74362

Gnomad4 AFR AF: 0.540

Gnomad4 AMR AF: 0.925

Gnomad4 ASJ AF: 0.986

Gnomad4 EAS AF: 0.890

Gnomad4 SAS AF: 0.992

Gnomad4 FIN AF: 0.978

Gnomad4 NFE AF: 0.968

Gnomad4 OTH AF: 0.891

Alfa AF: 0.892 Hom.: 7749

Bravo AF: 0.826

Asia WGS AF: 0.926 AC: 3218 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.68
CADD	Benign	5.2
DANN	Benign	0.70

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: rs982019; hg19: chr9-17613440;