rs7677704

Variant names:

• chr4-169162399-G-A
• rs7677704
• NM_020870.4:c.394-5720C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_020870.4(SH3RF1):​c.394-5720C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.319 in 151,946 control chromosomes in the GnomAD database, including 8,035 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: 32)
• Consequence: SH3RF1 NM_020870.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.259
• Publications: 1 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=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.395 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SH3RF1	NM_020870.4	c.394-5720C>T		intron_variant	Intron 2 of 11	ENST00000284637.14	NP_065921.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SH3RF1	ENST00000284637.14	c.394-5720C>T		intron_variant	Intron 2 of 11	1	NM_020870.4	ENSP00000284637.9
SH3RF1	ENST00000508685.1	n.275-5720C>T		intron_variant	Intron 1 of 8	1

Frequencies

GnomAD3 genomes AF: 0.319 AC: 48409 AN: 151828 Hom.: 8023 Cov.: 32

Gnomad AFR AF: 0.399

Gnomad AMI AF: 0.390

Gnomad AMR AF: 0.214

Gnomad ASJ AF: 0.255

Gnomad EAS AF: 0.105

Gnomad SAS AF: 0.278

Gnomad FIN AF: 0.295

Gnomad MID AF: 0.231

Gnomad NFE AF: 0.320

Gnomad OTH AF: 0.292

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

GnomAD4 genome AF: 0.319 AC: 48456 AN: 151946 Hom.: 8035 Cov.: 32 AF XY: 0.316 AC XY: 23442 AN XY: 74260

African (AFR) AF: 0.400 AC: 16568 AN: 41450

American (AMR) AF: 0.214 AC: 3265 AN: 15252

Ashkenazi Jewish (ASJ) AF: 0.255 AC: 886 AN: 3470

East Asian (EAS) AF: 0.105 AC: 543 AN: 5174

South Asian (SAS) AF: 0.275 AC: 1324 AN: 4814

European-Finnish (FIN) AF: 0.295 AC: 3114 AN: 10546

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

European-Non Finnish (NFE) AF: 0.320 AC: 21731 AN: 67934

Other (OTH) AF: 0.288 AC: 607 AN: 2106

Alfa AF: 0.330 Hom.: 1060

Bravo AF: 0.315

Asia WGS AF: 0.237 AC: 826 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	2.1
DANN	Benign	0.44
PhyloP100		0.26
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: rs7677704; hg19: chr4-170083550;