7-2354993-G-A

Variant names:

• chr7-2354993-G-A
• rs770420770
• NM_001037283.2:c.72G>A

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BS1 BS2

The NM_001037283.2(EIF3B):​c.72G>A​(p.Pro24Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00252 in 1,172,694 control chromosomes in the GnomAD database, including 27 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0089 (17 hom., cov: 32)
  • Exomes 𝑓: 0.0016 (10 hom.)
• Consequence: EIF3B NM_001037283.2 synonymous
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.00500

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]

ACMG classification

Verdict is Benign. Variant got -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.67).
• BP6: Variant 7-2354993-G-A is Benign according to our data. Variant chr7-2354993-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 787313.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-0.005 with no splicing effect.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00892 (1333/149418) while in subpopulation AFR AF= 0.0263 (1084/41236). AF 95% confidence interval is 0.025. There are 17 homozygotes in gnomad4. There are 649 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High AC in GnomAd4 at 1333 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EIF3B	NM_001037283.2	c.72G>A	p.Pro24Pro	synonymous_variant	Exon 1 of 19	ENST00000360876.9	NP_001032360.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
EIF3B	ENST00000360876.9	c.72G>A	p.Pro24Pro	synonymous_variant	Exon 1 of 19	1	NM_001037283.2	ENSP00000354125.4
EIF3B	ENST00000397011.2	c.72G>A	p.Pro24Pro	synonymous_variant	Exon 1 of 19	1		ENSP00000380206.2
EIF3B	ENST00000413917.5	c.72G>A	p.Pro24Pro	synonymous_variant	Exon 1 of 7	2		ENSP00000407785.1
EIF3B	ENST00000431643.5	c.-504-241G>A		intron_variant	Intron 1 of 7	5		ENSP00000408062.1

Frequencies

GnomAD3 genomes AF: 0.00891 AC: 1331 AN: 149310 Hom.: 17 Cov.: 32

Gnomad AFR AF: 0.0263

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00813

Gnomad ASJ AF: 0.00117

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00104

Gnomad FIN AF: 0.000104

Gnomad MID AF: 0.00321

Gnomad NFE AF: 0.00145

Gnomad OTH AF: 0.0102

GnomAD4 exome AF: 0.00159 AC: 1625 AN: 1023276 Hom.: 10 Cov.: 29 AF XY: 0.00152 AC XY: 740 AN XY: 488212

Gnomad4 AFR exome AF: 0.0273

Gnomad4 AMR exome AF: 0.00585

Gnomad4 ASJ exome AF: 0.00200

Gnomad4 EAS exome AF: 0.0000521

Gnomad4 SAS exome AF: 0.000188

Gnomad4 FIN exome AF: 0.000233

Gnomad4 NFE exome AF: 0.000965

Gnomad4 OTH exome AF: 0.00343

GnomAD4 genome AF: 0.00892 AC: 1333 AN: 149418 Hom.: 17 Cov.: 32 AF XY: 0.00890 AC XY: 649 AN XY: 72944

Gnomad4 AFR AF: 0.0263

Gnomad4 AMR AF: 0.00812

Gnomad4 ASJ AF: 0.00117

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000832

Gnomad4 FIN AF: 0.000104

Gnomad4 NFE AF: 0.00145

Gnomad4 OTH AF: 0.0101

Alfa AF: 0.00588 Hom.: 0

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

May 18, 2018

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.67
CADD	Benign	12
DANN	Benign	0.90
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		2.3

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: rs770420770; hg19: chr7-2394628;