NM_001037283.2:c.72G>A

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 0 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]

ACMG classification

Our verdict: Benign. The variant received -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 VariationId 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 the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High AC in GnomAd4 at 1333 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001037283.2. 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_001037283.2	MANE Select	c.72G>A	p.Pro24Pro	synonymous	Exon 1 of 19	NP_001032360.1	P55884-1
	EIF3B	NM_001362791.2		c.72G>A	p.Pro24Pro	synonymous	Exon 1 of 19	NP_001349720.1	P55884-1
	EIF3B	NM_003751.4		c.72G>A	p.Pro24Pro	synonymous	Exon 1 of 19	NP_003742.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EIF3B	ENST00000360876.9	TSL:1 MANE Select	c.72G>A	p.Pro24Pro	synonymous	Exon 1 of 19	ENSP00000354125.4	P55884-1
	EIF3B	ENST00000397011.2	TSL:1	c.72G>A	p.Pro24Pro	synonymous	Exon 1 of 19	ENSP00000380206.2	P55884-1
	EIF3B	ENST00000899983.1		c.72G>A	p.Pro24Pro	synonymous	Exon 1 of 19	ENSP00000570042.1

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

GnomAD2 exomes AF: 0.00 AC: 0 AN: 102 AF XY: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

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

African (AFR) AF: 0.0273 AC: 555 AN: 20332

American (AMR) AF: 0.00585 AC: 35 AN: 5988

Ashkenazi Jewish (ASJ) AF: 0.00200 AC: 22 AN: 10996

East Asian (EAS) AF: 0.0000521 AC: 1 AN: 19206

South Asian (SAS) AF: 0.000188 AC: 4 AN: 21278

European-Finnish (FIN) AF: 0.000233 AC: 4 AN: 17166

Middle Eastern (MID) AF: 0.00592 AC: 15 AN: 2534

European-Non Finnish (NFE) AF: 0.000965 AC: 856 AN: 886994

Other (OTH) AF: 0.00343 AC: 133 AN: 38782

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

African (AFR) AF: 0.0263 AC: 1084 AN: 41236

American (AMR) AF: 0.00812 AC: 122 AN: 15030

Ashkenazi Jewish (ASJ) AF: 0.00117 AC: 4 AN: 3432

East Asian (EAS) AF: 0.00 AC: 0 AN: 5114

South Asian (SAS) AF: 0.000832 AC: 4 AN: 4806

European-Finnish (FIN) AF: 0.000104 AC: 1 AN: 9590

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 292

European-Non Finnish (NFE) AF: 0.00145 AC: 97 AN: 66936

Other (OTH) AF: 0.0101 AC: 21 AN: 2072

Alfa AF: 0.00588 Hom.: 0

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.67
CADD	Benign	12
DANN	Benign	0.90
PhyloP100		-0.0050
PromoterAI		-0.0087	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		2.3
Mutation Taster		=100/0	polymorphism

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: rs770420770; hg19: chr7-2394628;