rs11205415

Variant names:

• chr1-248826485-T-G
• rs11205415
• ENST00000870257.1:c.-1550A>C

Variant summary

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

The ENST00000870257.1(SH3BP5L):​c.-1550A>C variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.248 in 154,760 control chromosomes in the GnomAD database, including 8,558 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 0.25 (8499 hom., cov: 32)
  • Exomes 𝑓: 0.19 (59 hom.)
• Consequence: SH3BP5L ENST00000870257.1 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.865
• Publications: 14 publications found

Genes affected

SH3BP5L (HGNC:29360): (SH3 binding domain protein 5 like) Enables guanyl-nucleotide exchange factor activity. Predicted to be involved in intracellular signal transduction and negative regulation of protein tyrosine kinase activity. Predicted to be active in cytoplasm. [provided by Alliance of Genome Resources, Apr 2022]

ENSG00000309922 (HGNC:):

MIR3124 (HGNC:38262): (microRNA 3124) microRNAs (miRNAs) are short (20-24 nt) non-coding RNAs that are involved in post-transcriptional regulation of gene expression in multicellular organisms by affecting both the stability and translation of mRNAs. miRNAs are transcribed by RNA polymerase II as part of capped and polyadenylated primary transcripts (pri-miRNAs) that can be either protein-coding or non-coding. The primary transcript is cleaved by the Drosha ribonuclease III enzyme to produce an approximately 70-nt stem-loop precursor miRNA (pre-miRNA), which is further cleaved by the cytoplasmic Dicer ribonuclease to generate the mature miRNA and antisense miRNA star (miRNA*) products. The mature miRNA is incorporated into a RNA-induced silencing complex (RISC), which recognizes target mRNAs through imperfect base pairing with the miRNA and most commonly results in translational inhibition or destabilization of the target mRNA. The RefSeq represents the predicted microRNA stem-loop. [provided by RefSeq, Sep 2009]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.98).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.566 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000870257.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MIR3124	NR_036070.1		n.*42T>G		downstream_gene	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SH3BP5L	ENST00000870257.1		c.-1550A>C		5_prime_UTR	Exon 1 of 6	ENSP00000540316.1
	ENSG00000309922	ENST00000845987.1		n.157T>G		non_coding_transcript_exon	Exon 1 of 1
	MIR3124	ENST00000582636.1	TSL:6	n.*42T>G		downstream_gene	N/A

Frequencies

GnomAD3 genomes AF: 0.249 AC: 37857 AN: 152024 Hom.: 8477 Cov.: 32

Gnomad AFR AF: 0.572

Gnomad AMI AF: 0.0208

Gnomad AMR AF: 0.177

Gnomad ASJ AF: 0.0992

Gnomad EAS AF: 0.534

Gnomad SAS AF: 0.290

Gnomad FIN AF: 0.0823

Gnomad MID AF: 0.155

Gnomad NFE AF: 0.0828

Gnomad OTH AF: 0.202

GnomAD2 exomes AF: 0.128 AC: 842 AN: 6578 AF XY: 0.104

Gnomad AFR exome AF: 0.616

Gnomad AMR exome AF: 0.246

Gnomad ASJ exome AF: 0.0931

Gnomad EAS exome AF: 0.600

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0859

Gnomad OTH exome AF: 0.190

GnomAD4 exome AF: 0.194 AC: 509 AN: 2618 Hom.: 59 Cov.: 0 AF XY: 0.186 AC XY: 251 AN XY: 1346

African (AFR) AF: 0.486 AC: 36 AN: 74

American (AMR) AF: 0.750 AC: 6 AN: 8

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 4

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AF: 0.196 AC: 18 AN: 92

European-Finnish (FIN) AF: 0.0701 AC: 30 AN: 428

Middle Eastern (MID) AF: 0.207 AC: 337 AN: 1630

European-Non Finnish (NFE) AF: 0.0798 AC: 15 AN: 188

Other (OTH) AF: 0.345 AC: 67 AN: 194

GnomAD4 genome AF: 0.249 AC: 37929 AN: 152142 Hom.: 8499 Cov.: 32 AF XY: 0.251 AC XY: 18656 AN XY: 74402

African (AFR) AF: 0.572 AC: 23728 AN: 41450

American (AMR) AF: 0.177 AC: 2712 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.0992 AC: 344 AN: 3468

East Asian (EAS) AF: 0.534 AC: 2759 AN: 5170

South Asian (SAS) AF: 0.289 AC: 1392 AN: 4824

European-Finnish (FIN) AF: 0.0823 AC: 874 AN: 10624

Middle Eastern (MID) AF: 0.150 AC: 44 AN: 294

European-Non Finnish (NFE) AF: 0.0828 AC: 5631 AN: 68000

Other (OTH) AF: 0.202 AC: 426 AN: 2108

Alfa AF: 0.194 Hom.: 5955

Bravo AF: 0.273

Asia WGS AF: 0.441 AC: 1528 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	3.8
DANN	Benign	0.72
PhyloP100		-0.86
Mutation Taster		=300/0	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: rs11205415; hg19: chr1-249120684; COSMIC: COSV63539586; COSMIC: COSV63539586;