rs2301942

Variant names:

• chr7-2354661-C-T
• rs2301942
• ENST00000922848.1:c.-261C>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+466C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.428 in 152,090 control chromosomes in the GnomAD database, including 15,687 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.43 (15687 hom., cov: 32)
• Consequence: EIF3B NM_001362792.2 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.0590
• Publications: 4 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=-1.01).
• BP6: Variant 7-2354661-C-T is Benign according to our data. Variant chr7-2354661-C-T is described in ClinVar as Benign. ClinVar VariationId is 1226868.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.555 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+466C>T		intron	N/A	NP_001349721.1
	EIF3B	NM_001362793.2		c.-505+466C>T		intron	N/A	NP_001349722.1
	EIF3B	NM_001037283.2	MANE Select	c.-261C>T		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.-261C>T		5_prime_UTR	Exon 2 of 20	ENSP00000592907.1
	EIF3B	ENST00000922849.1		c.-261C>T		5_prime_UTR	Exon 1 of 19	ENSP00000592908.1
	EIF3B	ENST00000431643.5	TSL:5	c.-505+466C>T		intron	N/A	ENSP00000408062.1	C9JQN7

Frequencies

GnomAD3 genomes AF: 0.429 AC: 65144 AN: 151972 Hom.: 15681 Cov.: 32

Gnomad AFR AF: 0.201

Gnomad AMI AF: 0.491

Gnomad AMR AF: 0.537

Gnomad ASJ AF: 0.507

Gnomad EAS AF: 0.571

Gnomad SAS AF: 0.380

Gnomad FIN AF: 0.468

Gnomad MID AF: 0.411

Gnomad NFE AF: 0.524

Gnomad OTH AF: 0.442

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

GnomAD4 genome AF: 0.428 AC: 65160 AN: 152090 Hom.: 15687 Cov.: 32 AF XY: 0.427 AC XY: 31784 AN XY: 74372

African (AFR) AF: 0.200 AC: 8320 AN: 41502

American (AMR) AF: 0.537 AC: 8213 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.507 AC: 1760 AN: 3470

East Asian (EAS) AF: 0.572 AC: 2951 AN: 5156

South Asian (SAS) AF: 0.381 AC: 1839 AN: 4828

European-Finnish (FIN) AF: 0.468 AC: 4956 AN: 10594

Middle Eastern (MID) AF: 0.414 AC: 121 AN: 292

European-Non Finnish (NFE) AF: 0.524 AC: 35628 AN: 67950

Other (OTH) AF: 0.439 AC: 925 AN: 2108

Alfa AF: 0.491 Hom.: 7441

Bravo AF: 0.430

Asia WGS AF: 0.387 AC: 1342 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	2.1
DANN	Benign	0.69
PhyloP100		-0.059
PromoterAI		-0.012	Neutral

Splicing

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

Other links and lift over

dbSNP: rs2301942; hg19: chr7-2394296;