NM_020870.4:c.393+16614T>C

Variant names:

• chr4-169252206-A-G
• rs17544750
• NM_020870.4:c.393+16614T>C

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+16614T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.176 in 152,254 control chromosomes in the GnomAD database, including 2,861 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 0.18 (2861 hom., cov: 32)
• Consequence: SH3RF1 NM_020870.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0190
• 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]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.244 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SH3RF1	NM_020870.4	MANE Select	c.393+16614T>C		intron	N/A	NP_065921.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SH3RF1	ENST00000284637.14	TSL:1 MANE Select	c.393+16614T>C		intron	N/A	ENSP00000284637.9
	SH3RF1	ENST00000508685.1	TSL:1	n.274+16614T>C		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.176 AC: 26759 AN: 152134 Hom.: 2866 Cov.: 32

Gnomad AFR AF: 0.0577

Gnomad AMI AF: 0.279

Gnomad AMR AF: 0.177

Gnomad ASJ AF: 0.212

Gnomad EAS AF: 0.0785

Gnomad SAS AF: 0.109

Gnomad FIN AF: 0.233

Gnomad MID AF: 0.142

Gnomad NFE AF: 0.247

Gnomad OTH AF: 0.208

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

GnomAD4 genome AF: 0.176 AC: 26746 AN: 152254 Hom.: 2861 Cov.: 32 AF XY: 0.174 AC XY: 12970 AN XY: 74434

African (AFR) AF: 0.0575 AC: 2390 AN: 41576

American (AMR) AF: 0.177 AC: 2703 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.212 AC: 736 AN: 3468

East Asian (EAS) AF: 0.0786 AC: 408 AN: 5188

South Asian (SAS) AF: 0.109 AC: 524 AN: 4828

European-Finnish (FIN) AF: 0.233 AC: 2470 AN: 10594

Middle Eastern (MID) AF: 0.143 AC: 42 AN: 294

European-Non Finnish (NFE) AF: 0.247 AC: 16785 AN: 68000

Other (OTH) AF: 0.206 AC: 435 AN: 2108

Alfa AF: 0.197 Hom.: 581

Bravo AF: 0.168

Asia WGS AF: 0.0890 AC: 310 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	5.0
DANN	Benign	0.32
PhyloP100		0.019
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: rs17544750; hg19: chr4-170173357;