5-146000534-A-G

Variant names:

• chr5-146000534-A-G
• rs2400207
• NM_152550.4:c.648+207A>G

Variant summary

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

The NM_152550.4(SH3RF2):​c.648+207A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.563 in 152,054 control chromosomes in the GnomAD database, including 24,763 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 0.56 (24763 hom., cov: 33)
• Consequence: SH3RF2 NM_152550.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.557
• Publications: 3 publications found

Genes affected

SH3RF2 (HGNC:26299): (SH3 domain containing ring finger 2) Enables protein phosphatase 1 binding activity and ubiquitin protein ligase activity. Involved in several processes, including positive regulation of JNK cascade; protein autoubiquitination; and regulation of cellular protein metabolic process. Located in nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

LOC107986458 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.768 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SH3RF2	NM_152550.4	c.648+207A>G		intron_variant	Intron 3 of 9	ENST00000359120.9	NP_689763.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SH3RF2	ENST00000359120.9	c.648+207A>G		intron_variant	Intron 3 of 9	1	NM_152550.4	ENSP00000352028.4
SH3RF2	ENST00000511217.1	c.648+207A>G		intron_variant	Intron 2 of 9	1		ENSP00000424497.1

Frequencies

GnomAD3 genomes AF: 0.563 AC: 85594 AN: 151938 Hom.: 24763 Cov.: 33

Gnomad AFR AF: 0.451

Gnomad AMI AF: 0.523

Gnomad AMR AF: 0.595

Gnomad ASJ AF: 0.665

Gnomad EAS AF: 0.714

Gnomad SAS AF: 0.790

Gnomad FIN AF: 0.566

Gnomad MID AF: 0.790

Gnomad NFE AF: 0.589

Gnomad OTH AF: 0.626

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

GnomAD4 genome AF: 0.563 AC: 85627 AN: 152054 Hom.: 24763 Cov.: 33 AF XY: 0.571 AC XY: 42423 AN XY: 74310

African (AFR) AF: 0.451 AC: 18713 AN: 41468

American (AMR) AF: 0.594 AC: 9076 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.665 AC: 2308 AN: 3470

East Asian (EAS) AF: 0.714 AC: 3701 AN: 5184

South Asian (SAS) AF: 0.789 AC: 3799 AN: 4816

European-Finnish (FIN) AF: 0.566 AC: 5958 AN: 10528

Middle Eastern (MID) AF: 0.788 AC: 230 AN: 292

European-Non Finnish (NFE) AF: 0.589 AC: 40032 AN: 67994

Other (OTH) AF: 0.630 AC: 1334 AN: 2116

Alfa AF: 0.561 Hom.: 3959

Bravo AF: 0.554

Asia WGS AF: 0.735 AC: 2548 AN: 3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	1.1
DANN	Benign	0.28
PhyloP100		-0.56
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: rs2400207; hg19: chr5-145380097;