rs9312445

Variant names:

• chr4-169156281-A-G
• rs9312445
• NM_020870.4:c.669+123T>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.669+123T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.292 in 1,085,350 control chromosomes in the GnomAD database, including 48,372 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 0.32 (8035 hom., cov: 33)
  • Exomes 𝑓: 0.29 (40337 hom.)
• Consequence: SH3RF1 NM_020870.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.515
• 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=-0.85).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.394 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SH3RF1	NM_020870.4	c.669+123T>C		intron_variant	Intron 3 of 11	ENST00000284637.14	NP_065921.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SH3RF1	ENST00000284637.14	c.669+123T>C		intron_variant	Intron 3 of 11	1	NM_020870.4	ENSP00000284637.9
SH3RF1	ENST00000508685.1	n.550+123T>C		intron_variant	Intron 2 of 8	1
SH3RF1	ENST00000511421.5	n.252+123T>C		intron_variant	Intron 1 of 7	1		ENSP00000426418.1

Frequencies

GnomAD3 genomes AF: 0.318 AC: 48403 AN: 151972 Hom.: 8022 Cov.: 33

Gnomad AFR AF: 0.399

Gnomad AMI AF: 0.387

Gnomad AMR AF: 0.214

Gnomad ASJ AF: 0.255

Gnomad EAS AF: 0.105

Gnomad SAS AF: 0.276

Gnomad FIN AF: 0.293

Gnomad MID AF: 0.231

Gnomad NFE AF: 0.320

Gnomad OTH AF: 0.288

GnomAD4 exome AF: 0.288 AC: 268557 AN: 933258 Hom.: 40337 AF XY: 0.288 AC XY: 132720 AN XY: 461162

African (AFR) AF: 0.401 AC: 8751 AN: 21832

American (AMR) AF: 0.168 AC: 3758 AN: 22426

Ashkenazi Jewish (ASJ) AF: 0.260 AC: 4147 AN: 15954

East Asian (EAS) AF: 0.115 AC: 4087 AN: 35608

South Asian (SAS) AF: 0.269 AC: 10678 AN: 39630

European-Finnish (FIN) AF: 0.287 AC: 12398 AN: 43266

Middle Eastern (MID) AF: 0.268 AC: 808 AN: 3016

European-Non Finnish (NFE) AF: 0.299 AC: 212290 AN: 710402

Other (OTH) AF: 0.283 AC: 11640 AN: 41124

GnomAD4 genome AF: 0.319 AC: 48453 AN: 152092 Hom.: 8035 Cov.: 33 AF XY: 0.315 AC XY: 23443 AN XY: 74350

African (AFR) AF: 0.400 AC: 16569 AN: 41472

American (AMR) AF: 0.214 AC: 3263 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.255 AC: 884 AN: 3468

East Asian (EAS) AF: 0.105 AC: 547 AN: 5188

South Asian (SAS) AF: 0.274 AC: 1323 AN: 4830

European-Finnish (FIN) AF: 0.293 AC: 3095 AN: 10562

Middle Eastern (MID) AF: 0.221 AC: 65 AN: 294

European-Non Finnish (NFE) AF: 0.320 AC: 21754 AN: 67976

Other (OTH) AF: 0.285 AC: 601 AN: 2110

Alfa AF: 0.330 Hom.: 1061

Bravo AF: 0.315

Asia WGS AF: 0.236 AC: 822 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	11
DANN	Benign	0.51
PhyloP100		0.52
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.080		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: rs9312445; hg19: chr4-170077432; COSMIC: COSV52919971;