9-17607039-G-A

Position:

• chr9-17607039-G-A

Variant summary

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

The NM_003026.5(SH3GL2):​c.45+27752G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.11 in 152,184 control chromosomes in the GnomAD database, including 3,083 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 0.11 (3083 hom., cov: 32)
• Consequence: SH3GL2 NM_003026.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.726

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=-0.93).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.377 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SH3GL2	NM_003026.5	c.45+27752G>A		intron_variant		ENST00000380607.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SH3GL2	ENST00000380607.5	c.45+27752G>A		intron_variant		1	NM_003026.5	P1
SH3GL2	ENST00000467085.1	n.207-23315G>A		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.110 AC: 16679 AN: 152066 Hom.: 3084 Cov.: 32

Gnomad AFR AF: 0.383

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0387

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00135

Gnomad SAS AF: 0.00207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0158

Gnomad NFE AF: 0.00118

Gnomad OTH AF: 0.0760

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

GnomAD4 genome AF: 0.110 AC: 16706 AN: 152184 Hom.: 3083 Cov.: 32 AF XY: 0.104 AC XY: 7767 AN XY: 74420

Gnomad4 AFR AF: 0.382

Gnomad4 AMR AF: 0.0387

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00135

Gnomad4 SAS AF: 0.00166

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00118

Gnomad4 OTH AF: 0.0752

Alfa AF: 0.0359 Hom.: 105

Bravo AF: 0.126

Asia WGS AF: 0.0230 AC: 82 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	5.6
DANN	Benign	0.66

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: rs7034773; hg19: chr9-17607037;