rs243404

Variant names:

• chr19-4384677-G-A
• rs243404
• NM_003025.4:c.45+15647C>T

Your query was ambiguous. Multiple possible variants found:

• chr19-4384677-G-A
• chr19-4384677-G-T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_003025.4(SH3GL1):​c.45+15647C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.27 in 152,078 control chromosomes in the GnomAD database, including 6,413 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 0.27 (6413 hom., cov: 32)
• Consequence: SH3GL1 NM_003025.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.677
• Publications: 16 publications found

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]

SH3GL1 Gene-Disease associations (from GenCC):

• immunodeficiency disease

  Inheritance: AR Classification: LIMITED Submitted by: Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.573 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003025.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SH3GL1	NM_003025.4	MANE Select	c.45+15647C>T		intron	N/A	NP_003016.1
	SH3GL1	NM_001199943.2		c.45+15647C>T		intron	N/A	NP_001186872.1
	SH3GL1	NM_001199944.2		c.45+15647C>T		intron	N/A	NP_001186873.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SH3GL1	ENST00000269886.7	TSL:1 MANE Select	c.45+15647C>T		intron	N/A	ENSP00000269886.2
	SH3GL1	ENST00000908568.1		c.45+15647C>T		intron	N/A	ENSP00000578627.1
	SH3GL1	ENST00000945946.1		c.45+15647C>T		intron	N/A	ENSP00000616005.1

Frequencies

GnomAD3 genomes AF: 0.270 AC: 41088 AN: 151960 Hom.: 6400 Cov.: 32

Gnomad AFR AF: 0.148

Gnomad AMI AF: 0.412

Gnomad AMR AF: 0.401

Gnomad ASJ AF: 0.323

Gnomad EAS AF: 0.590

Gnomad SAS AF: 0.353

Gnomad FIN AF: 0.335

Gnomad MID AF: 0.361

Gnomad NFE AF: 0.270

Gnomad OTH AF: 0.294

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

GnomAD4 genome AF: 0.270 AC: 41116 AN: 152078 Hom.: 6413 Cov.: 32 AF XY: 0.278 AC XY: 20673 AN XY: 74340

African (AFR) AF: 0.148 AC: 6127 AN: 41512

American (AMR) AF: 0.402 AC: 6148 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.323 AC: 1120 AN: 3468

East Asian (EAS) AF: 0.591 AC: 3050 AN: 5162

South Asian (SAS) AF: 0.353 AC: 1701 AN: 4822

European-Finnish (FIN) AF: 0.335 AC: 3535 AN: 10566

Middle Eastern (MID) AF: 0.350 AC: 103 AN: 294

European-Non Finnish (NFE) AF: 0.270 AC: 18341 AN: 67964

Other (OTH) AF: 0.293 AC: 619 AN: 2110

Alfa AF: 0.282 Hom.: 12688

Bravo AF: 0.273

Asia WGS AF: 0.447 AC: 1551 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	1.2
DANN	Benign	0.88
PhyloP100		-0.68
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs243404; hg19: chr19-4384674;