NM_001037283.2:c.190T>C

Variant names:

• chr7-2355111-T-C
• rs9690787
• NM_001037283.2:c.190T>C

Variant summary

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

The NM_001037283.2(EIF3B):​c.190T>C​(p.Ser64Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.782 in 1,369,888 control chromosomes in the GnomAD database, including 419,783 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.75 (42752 hom., cov: 30)
  • Exomes 𝑓: 0.79 (377031 hom.)
• Consequence: EIF3B NM_001037283.2 missense
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.231
• Publications: 28 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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=8.095357E-7).
• BP6: Variant 7-2355111-T-C is Benign according to our data. Variant chr7-2355111-T-C is described in ClinVar as Benign. ClinVar VariationId is 1294679.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.843 is higher than 0.05.

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.190T>C	p.Ser64Pro	missense	Exon 1 of 19	NP_001032360.1	P55884-1
	EIF3B	NM_001362791.2		c.190T>C	p.Ser64Pro	missense	Exon 1 of 19	NP_001349720.1	P55884-1
	EIF3B	NM_003751.4		c.190T>C	p.Ser64Pro	missense	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.190T>C	p.Ser64Pro	missense	Exon 1 of 19	ENSP00000354125.4	P55884-1
	EIF3B	ENST00000397011.2	TSL:1	c.190T>C	p.Ser64Pro	missense	Exon 1 of 19	ENSP00000380206.2	P55884-1
	EIF3B	ENST00000899983.1		c.190T>C	p.Ser64Pro	missense	Exon 1 of 19	ENSP00000570042.1

Frequencies

GnomAD3 genomes AF: 0.751 AC: 113095 AN: 150644 Hom.: 42714 Cov.: 30

Gnomad AFR AF: 0.642

Gnomad AMI AF: 0.651

Gnomad AMR AF: 0.769

Gnomad ASJ AF: 0.754

Gnomad EAS AF: 0.863

Gnomad SAS AF: 0.792

Gnomad FIN AF: 0.838

Gnomad MID AF: 0.645

Gnomad NFE AF: 0.789

Gnomad OTH AF: 0.753

GnomAD2 exomes AF: 0.712 AC: 9445 AN: 13272 AF XY: 0.722

Gnomad AFR exome AF: 0.587

Gnomad AMR exome AF: 0.706

Gnomad ASJ exome AF: 0.655

Gnomad EAS exome AF: 0.728

Gnomad FIN exome AF: 0.798

Gnomad NFE exome AF: 0.719

Gnomad OTH exome AF: 0.691

GnomAD4 exome AF: 0.786 AC: 957921 AN: 1219138 Hom.: 377031 Cov.: 56 AF XY: 0.785 AC XY: 467241 AN XY: 595144

African (AFR) AF: 0.631 AC: 15034 AN: 23842

American (AMR) AF: 0.775 AC: 8221 AN: 10612

Ashkenazi Jewish (ASJ) AF: 0.751 AC: 12979 AN: 17272

East Asian (EAS) AF: 0.827 AC: 22446 AN: 27126

South Asian (SAS) AF: 0.776 AC: 42997 AN: 55382

European-Finnish (FIN) AF: 0.831 AC: 24234 AN: 29148

Middle Eastern (MID) AF: 0.682 AC: 2354 AN: 3452

European-Non Finnish (NFE) AF: 0.789 AC: 791151 AN: 1002538

Other (OTH) AF: 0.774 AC: 38505 AN: 49766

GnomAD4 genome AF: 0.751 AC: 113184 AN: 150750 Hom.: 42752 Cov.: 30 AF XY: 0.754 AC XY: 55576 AN XY: 73682

African (AFR) AF: 0.642 AC: 26422 AN: 41134

American (AMR) AF: 0.769 AC: 11685 AN: 15196

Ashkenazi Jewish (ASJ) AF: 0.754 AC: 2602 AN: 3452

East Asian (EAS) AF: 0.864 AC: 4370 AN: 5058

South Asian (SAS) AF: 0.794 AC: 3811 AN: 4800

European-Finnish (FIN) AF: 0.838 AC: 8688 AN: 10362

Middle Eastern (MID) AF: 0.642 AC: 185 AN: 288

European-Non Finnish (NFE) AF: 0.789 AC: 53256 AN: 67470

Other (OTH) AF: 0.755 AC: 1583 AN: 2096

Alfa AF: 0.767 Hom.: 5356

Bravo AF: 0.742

TwinsUK AF: 0.801 AC: 2970

ALSPAC AF: 0.795 AC: 3063

ExAC AF: 0.582 AC: 7258

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
AlphaMissense	Benign	0.053
BayesDel_addAF	Benign	-0.66	T
BayesDel_noAF	Benign	-0.58
CADD	Benign	9.5
DANN	Benign	0.39
DEOGEN2	Benign	0.017	T
Eigen	Benign	-1.7
Eigen_PC	Benign	-1.6
FATHMM_MKL	Benign	0.00044	N
LIST_S2	Benign	0.097	T
MetaRNN	Benign	8.1e-7	T
MetaSVM	Benign	-0.96	T
MutationAssessor	Benign	-0.69	N
PhyloP100		-0.23
PrimateAI	Uncertain	0.69	T
PROVEAN	Benign	0.37	N
REVEL	Benign	0.076
Sift	Benign	1.0	T
Sift4G	Benign	0.91	T
Polyphen		0.0	B
Vest4		0.026
MPC		0.47
ClinPred		0.00016	T
GERP RS		0.18
PromoterAI		0.038	Neutral
Varity_R		0.039
gMVP		0.11
Mutation Taster		=100/0	polymorphism (auto)

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: rs9690787; hg19: chr7-2394746; COSMIC: COSV62803084; COSMIC: COSV62803084;