rs2301943

Variant names:

• chr7-2354681-C-G
• rs2301943
• ENST00000922848.1:c.-241C>G

Your query was ambiguous. Multiple possible variants found:

• chr7-2354681-C-G
• chr7-2354681-C-T

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_001362792.2(EIF3B):​c.-505+486C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.223 in 152,160 control chromosomes in the GnomAD database, including 4,315 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.22 (4315 hom., cov: 32)
• Consequence: EIF3B NM_001362792.2 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.166
• Publications: 5 publications found

Genes affected

EIF3B (HGNC:3280): (eukaryotic translation initiation factor 3 subunit B) Enables RNA binding activity. Contributes to translation initiation factor activity. Involved in several processes, including IRES-dependent viral translational initiation; translational initiation; and viral translational termination-reinitiation. Located in extracellular exosome. Part of eukaryotic translation initiation factor 3 complex. [provided by Alliance of Genome Resources, Apr 2022]

SNX8 (HGNC:14972): (sorting nexin 8) Enables identical protein binding activity and phosphatidylinositol binding activity. Involved in early endosome to Golgi transport and intracellular protein transport. Located in early endosome membrane. Colocalizes with retromer complex. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.03).
• BP6: Variant 7-2354681-C-G is Benign according to our data. Variant chr7-2354681-C-G is described in ClinVar as Benign. ClinVar VariationId is 1294697.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.375 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001362792.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EIF3B	NM_001362792.2		c.-505+486C>G		intron	N/A	NP_001349721.1
	EIF3B	NM_001362793.2		c.-505+486C>G		intron	N/A	NP_001349722.1
	EIF3B	NM_001037283.2	MANE Select	c.-241C>G		upstream_gene	N/A	NP_001032360.1	P55884-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EIF3B	ENST00000922848.1		c.-241C>G		5_prime_UTR	Exon 2 of 20	ENSP00000592907.1
	EIF3B	ENST00000922849.1		c.-241C>G		5_prime_UTR	Exon 1 of 19	ENSP00000592908.1
	EIF3B	ENST00000431643.5	TSL:5	c.-505+486C>G		intron	N/A	ENSP00000408062.1	C9JQN7

Frequencies

GnomAD3 genomes AF: 0.223 AC: 33847 AN: 152042 Hom.: 4309 Cov.: 32

Gnomad AFR AF: 0.105

Gnomad AMI AF: 0.157

Gnomad AMR AF: 0.189

Gnomad ASJ AF: 0.245

Gnomad EAS AF: 0.284

Gnomad SAS AF: 0.389

Gnomad FIN AF: 0.370

Gnomad MID AF: 0.215

Gnomad NFE AF: 0.262

Gnomad OTH AF: 0.224

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

GnomAD4 genome AF: 0.223 AC: 33871 AN: 152160 Hom.: 4315 Cov.: 32 AF XY: 0.230 AC XY: 17081 AN XY: 74378

African (AFR) AF: 0.105 AC: 4375 AN: 41544

American (AMR) AF: 0.189 AC: 2894 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.245 AC: 848 AN: 3466

East Asian (EAS) AF: 0.284 AC: 1466 AN: 5170

South Asian (SAS) AF: 0.390 AC: 1882 AN: 4824

European-Finnish (FIN) AF: 0.370 AC: 3904 AN: 10564

Middle Eastern (MID) AF: 0.214 AC: 63 AN: 294

European-Non Finnish (NFE) AF: 0.262 AC: 17807 AN: 67982

Other (OTH) AF: 0.231 AC: 489 AN: 2116

Alfa AF: 0.157 Hom.: 344

Bravo AF: 0.199

Asia WGS AF: 0.346 AC: 1207 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	2.9
DANN	Benign	0.52
PhyloP100		-0.17
PromoterAI		0.014	Neutral
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs2301943; hg19: chr7-2394316;