rs2069

Variant names:

• chr4-169124915-G-C
• rs2069
• NM_020870.4:c.1180-2649C>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.1180-2649C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0767 in 152,194 control chromosomes in the GnomAD database, including 617 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 0.077 (617 hom., cov: 32)
• Consequence: SH3RF1 NM_020870.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.318
• Publications: 5 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=-0.81).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.152 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SH3RF1	NM_020870.4	c.1180-2649C>G		intron_variant	Intron 6 of 11	ENST00000284637.14	NP_065921.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SH3RF1	ENST00000284637.14	c.1180-2649C>G		intron_variant	Intron 6 of 11	1	NM_020870.4	ENSP00000284637.9
SH3RF1	ENST00000508685.1	n.1061-2649C>G		intron_variant	Intron 5 of 8	1
SH3RF1	ENST00000511421.5	n.763-2716C>G		intron_variant	Intron 4 of 7	1		ENSP00000426418.1

Frequencies

GnomAD3 genomes AF: 0.0765 AC: 11634 AN: 152076 Hom.: 613 Cov.: 32

Gnomad AFR AF: 0.155

Gnomad AMI AF: 0.122

Gnomad AMR AF: 0.0486

Gnomad ASJ AF: 0.0358

Gnomad EAS AF: 0.0460

Gnomad SAS AF: 0.0222

Gnomad FIN AF: 0.0437

Gnomad MID AF: 0.0538

Gnomad NFE AF: 0.0484

Gnomad OTH AF: 0.0636

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

GnomAD4 genome AF: 0.0767 AC: 11670 AN: 152194 Hom.: 617 Cov.: 32 AF XY: 0.0753 AC XY: 5601 AN XY: 74406

African (AFR) AF: 0.155 AC: 6446 AN: 41492

American (AMR) AF: 0.0485 AC: 743 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.0358 AC: 124 AN: 3468

East Asian (EAS) AF: 0.0463 AC: 240 AN: 5182

South Asian (SAS) AF: 0.0220 AC: 106 AN: 4822

European-Finnish (FIN) AF: 0.0437 AC: 462 AN: 10578

Middle Eastern (MID) AF: 0.0408 AC: 12 AN: 294

European-Non Finnish (NFE) AF: 0.0484 AC: 3293 AN: 68030

Other (OTH) AF: 0.0630 AC: 133 AN: 2112

Alfa AF: 0.0649 Hom.: 49

Bravo AF: 0.0819

Asia WGS AF: 0.0510 AC: 179 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	7.7
DANN	Benign	0.57
PhyloP100		0.32
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: rs2069; hg19: chr4-170046066;