7-2354661-C-T

Variant names:

• chr7-2354661-C-T
• rs2301942
• XM_011515599.2:c.-261C>T

Variant summary

Our verdict is Benign. Variant got -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

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

Verdict is Benign. Variant got -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 id 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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EIF3B	NM_001037283.2	c.-261C>T		upstream_gene_variant		ENST00000360876.9	NP_001032360.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
EIF3B	ENST00000431643.5	c.-505+466C>T		intron_variant	Intron 1 of 7	5		ENSP00000408062.1
EIF3B	ENST00000360876.9	c.-261C>T		upstream_gene_variant		1	NM_001037283.2	ENSP00000354125.4
EIF3B	ENST00000397011.2	c.-261C>T		upstream_gene_variant		1		ENSP00000380206.2
EIF3B	ENST00000413917.5	c.-261C>T		upstream_gene_variant		2		ENSP00000407785.1

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

Gnomad4 AFR AF: 0.200

Gnomad4 AMR AF: 0.537

Gnomad4 ASJ AF: 0.507

Gnomad4 EAS AF: 0.572

Gnomad4 SAS AF: 0.381

Gnomad4 FIN AF: 0.468

Gnomad4 NFE AF: 0.524

Gnomad4 OTH AF: 0.439

Alfa AF: 0.495 Hom.: 6074

Bravo AF: 0.430

Asia WGS AF: 0.387 AC: 1342 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

May 11, 2021

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	2.1
DANN	Benign	0.69

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs2301942; hg19: chr7-2394296;