4-169215842-C-T

Variant names:

• chr4-169215842-C-T
• rs2706748
• NM_020870.4:c.393+52978G>A

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+52978G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.482 in 151,438 control chromosomes in the GnomAD database, including 18,534 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 0.48 (18534 hom., cov: 29)
• Consequence: SH3RF1 NM_020870.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.942
• Publications: 3 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]

ENSG00000251171 (HGNC:58426):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.758 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_020870.4. 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
	SH3RF1	NM_020870.4	MANE Select	c.393+52978G>A		intron	N/A	NP_065921.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SH3RF1	ENST00000284637.14	TSL:1 MANE Select	c.393+52978G>A		intron	N/A	ENSP00000284637.9
	SH3RF1	ENST00000508685.1	TSL:1	n.274+52978G>A		intron	N/A
	SH3RF1	ENST00000924372.1		c.393+52978G>A		intron	N/A	ENSP00000594431.1

Frequencies

GnomAD3 genomes AF: 0.482 AC: 72916 AN: 151322 Hom.: 18534 Cov.: 29

Gnomad AFR AF: 0.310

Gnomad AMI AF: 0.608

Gnomad AMR AF: 0.534

Gnomad ASJ AF: 0.607

Gnomad EAS AF: 0.779

Gnomad SAS AF: 0.542

Gnomad FIN AF: 0.525

Gnomad MID AF: 0.618

Gnomad NFE AF: 0.532

Gnomad OTH AF: 0.495

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

GnomAD4 genome AF: 0.482 AC: 72936 AN: 151438 Hom.: 18534 Cov.: 29 AF XY: 0.481 AC XY: 35555 AN XY: 73956

African (AFR) AF: 0.309 AC: 12739 AN: 41194

American (AMR) AF: 0.533 AC: 8123 AN: 15244

Ashkenazi Jewish (ASJ) AF: 0.607 AC: 2105 AN: 3466

East Asian (EAS) AF: 0.778 AC: 4022 AN: 5168

South Asian (SAS) AF: 0.545 AC: 2611 AN: 4794

European-Finnish (FIN) AF: 0.525 AC: 5453 AN: 10388

Middle Eastern (MID) AF: 0.616 AC: 180 AN: 292

European-Non Finnish (NFE) AF: 0.532 AC: 36102 AN: 67876

Other (OTH) AF: 0.498 AC: 1049 AN: 2108

Alfa AF: 0.494 Hom.: 2488

Bravo AF: 0.478

Asia WGS AF: 0.619 AC: 2152 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	1.5
DANN	Benign	0.45
PhyloP100		-0.94
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: rs2706748; hg19: chr4-170136993;