4-169244828-T-C

Variant names:

• chr4-169244828-T-C
• rs10518041
• NM_020870.4:c.393+23992A>G

Variant summary

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

The NM_020870.4(SH3RF1):​c.393+23992A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.388 in 152,070 control chromosomes in the GnomAD database, including 13,469 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 0.39 (13469 hom., cov: 33)
• Consequence: SH3RF1 NM_020870.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.557
• Publications: 2 publications found

Genes affected

SH3RF1 (HGNC:17650): (SH3 domain containing ring finger 1) This gene encodes a protein containing an N-terminus RING-finger, four SH3 domains, and a region implicated in binding of the Rho GTPase Rac. Via the RING-finger, the encoded protein has been shown to function as an ubiquitin-protein ligase involved in protein sorting at the trans-Golgi network. The encoded protein may also act as a scaffold for the c-Jun N-terminal kinase signaling pathway, facilitating the formation of a functional signaling module. [provided by RefSeq, Jul 2008]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.78).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.695 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SH3RF1	NM_020870.4	c.393+23992A>G		intron_variant	Intron 2 of 11	ENST00000284637.14	NP_065921.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SH3RF1	ENST00000284637.14	c.393+23992A>G		intron_variant	Intron 2 of 11	1	NM_020870.4	ENSP00000284637.9
SH3RF1	ENST00000508685.1	n.274+23992A>G		intron_variant	Intron 1 of 8	1

Frequencies

GnomAD3 genomes AF: 0.388 AC: 58927 AN: 151952 Hom.: 13470 Cov.: 33

Gnomad AFR AF: 0.136

Gnomad AMI AF: 0.487

Gnomad AMR AF: 0.397

Gnomad ASJ AF: 0.552

Gnomad EAS AF: 0.715

Gnomad SAS AF: 0.454

Gnomad FIN AF: 0.478

Gnomad MID AF: 0.576

Gnomad NFE AF: 0.484

Gnomad OTH AF: 0.415

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

GnomAD4 genome AF: 0.388 AC: 58931 AN: 152070 Hom.: 13469 Cov.: 33 AF XY: 0.386 AC XY: 28688 AN XY: 74316

African (AFR) AF: 0.136 AC: 5639 AN: 41524

American (AMR) AF: 0.397 AC: 6062 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.552 AC: 1914 AN: 3468

East Asian (EAS) AF: 0.714 AC: 3692 AN: 5170

South Asian (SAS) AF: 0.457 AC: 2198 AN: 4814

European-Finnish (FIN) AF: 0.478 AC: 5042 AN: 10544

Middle Eastern (MID) AF: 0.568 AC: 167 AN: 294

European-Non Finnish (NFE) AF: 0.484 AC: 32890 AN: 67956

Other (OTH) AF: 0.419 AC: 884 AN: 2110

Alfa AF: 0.460 Hom.: 12061

Bravo AF: 0.376

Asia WGS AF: 0.545 AC: 1889 AN: 3470

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	3.8
DANN	Benign	0.81
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: rs10518041; hg19: chr4-170165979;