chr4-169252206-A-G

Position:

• chr4-169252206-A-G

Variant summary

Our verdict is Benign. Variant got -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

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

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SH3RF1	NM_020870.4	c.393+16614T>C		intron_variant		ENST00000284637.14

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SH3RF1	ENST00000284637.14	c.393+16614T>C		intron_variant		1	NM_020870.4	P1
SH3RF1	ENST00000508685.1	n.274+16614T>C		intron_variant, non_coding_transcript_variant		1

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

Gnomad4 AFR AF: 0.0575

Gnomad4 AMR AF: 0.177

Gnomad4 ASJ AF: 0.212

Gnomad4 EAS AF: 0.0786

Gnomad4 SAS AF: 0.109

Gnomad4 FIN AF: 0.233

Gnomad4 NFE AF: 0.247

Gnomad4 OTH AF: 0.206

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 v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	5.0
DANN	Benign	0.32

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

Publications

LitVar

Other links and lift over

dbSNP: rs17544750; hg19: chr4-170173357;