chr19-4363292-C-T

Position:

• chr19-4363292-C-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_003025.4(SH3GL1):​c.728+78G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.241 in 1,081,548 control chromosomes in the GnomAD database, including 33,251 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.21 (3662 hom., cov: 34)
  • Exomes 𝑓: 0.25 (29589 hom.)
• Consequence: SH3GL1 NM_003025.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.53

Genes affected

SH3GL1 (HGNC:10830): (SH3 domain containing GRB2 like 1, endophilin A2) This gene encodes a member of the endophilin family of Src homology 3 domain-containing proteins. The encoded protein is involved in endocytosis and may also play a role in the cell cycle. Overexpression of this gene may play a role in leukemogenesis, and the encoded protein has been implicated in acute myeloid leukemia as a fusion partner of the myeloid-lymphoid leukemia protein. Pseudogenes of this gene are located on the long arm of chromosomes 11 and 17. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene. [provided by RefSeq, Jan 2011]

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.03).
• BP6: Variant 19-4363292-C-T is Benign according to our data. Variant chr19-4363292-C-T is described in ClinVar as [Benign]. Clinvar id is 1266548.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.269 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SH3GL1	NM_003025.4	c.728+78G>A		intron_variant		ENST00000269886.7	NP_003016.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SH3GL1	ENST00000269886.7	c.728+78G>A		intron_variant		1	NM_003025.4	ENSP00000269886.2
SH3GL1	ENST00000417295.6	c.584+78G>A		intron_variant		2		ENSP00000404568.2
SH3GL1	ENST00000598564.5	c.536+78G>A		intron_variant		2		ENSP00000470792.1

Frequencies

GnomAD3 genomes AF: 0.208 AC: 31649 AN: 152132 Hom.: 3662 Cov.: 34

Gnomad AFR AF: 0.105

Gnomad AMI AF: 0.183

Gnomad AMR AF: 0.276

Gnomad ASJ AF: 0.227

Gnomad EAS AF: 0.125

Gnomad SAS AF: 0.261

Gnomad FIN AF: 0.175

Gnomad MID AF: 0.184

Gnomad NFE AF: 0.262

Gnomad OTH AF: 0.229

GnomAD4 exome AF: 0.247 AC: 229181 AN: 929298 Hom.: 29589 AF XY: 0.247 AC XY: 117073 AN XY: 473822

Gnomad4 AFR exome AF: 0.0997

Gnomad4 AMR exome AF: 0.251

Gnomad4 ASJ exome AF: 0.227

Gnomad4 EAS exome AF: 0.107

Gnomad4 SAS exome AF: 0.256

Gnomad4 FIN exome AF: 0.184

Gnomad4 NFE exome AF: 0.263

Gnomad4 OTH exome AF: 0.249

GnomAD4 genome AF: 0.208 AC: 31657 AN: 152250 Hom.: 3662 Cov.: 34 AF XY: 0.207 AC XY: 15411 AN XY: 74432

Gnomad4 AFR AF: 0.105

Gnomad4 AMR AF: 0.275

Gnomad4 ASJ AF: 0.227

Gnomad4 EAS AF: 0.125

Gnomad4 SAS AF: 0.261

Gnomad4 FIN AF: 0.175

Gnomad4 NFE AF: 0.262

Gnomad4 OTH AF: 0.231

Alfa AF: 0.228 Hom.: 534

Bravo AF: 0.208

Asia WGS AF: 0.218 AC: 759 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 19, 2021	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.33
DANN	Benign	0.52

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: rs62129346; hg19: chr19-4363289; COSMIC: COSV53656992; COSMIC: COSV53656992;