7-2355111-T-C

Variant names:

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

Variant summary

Our verdict is Benign. Variant got -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. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★). Another nucleotide change resulting in the same amino acid substitution has been previously reported as Likely benign in UniProt.

• 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

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 -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 id 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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EIF3B	NM_001037283.2	c.190T>C	p.Ser64Pro	missense_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.190T>C	p.Ser64Pro	missense_variant	Exon 1 of 19	1	NM_001037283.2	ENSP00000354125.4
EIF3B	ENST00000397011.2	c.190T>C	p.Ser64Pro	missense_variant	Exon 1 of 19	1		ENSP00000380206.2
EIF3B	ENST00000413917.5	c.190T>C	p.Ser64Pro	missense_variant	Exon 1 of 7	2		ENSP00000407785.1
EIF3B	ENST00000431643.5	c.-504-123T>C		intron_variant	Intron 1 of 7	5		ENSP00000408062.1

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

GnomAD3 exomes AF: 0.712 AC: 9445 AN: 13272 Hom.: 3459 AF XY: 0.722 AC XY: 6200 AN XY: 8586

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 SAS exome AF: 0.708

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

Gnomad4 AFR exome AF: 0.631

Gnomad4 AMR exome AF: 0.775

Gnomad4 ASJ exome AF: 0.751

Gnomad4 EAS exome AF: 0.827

Gnomad4 SAS exome AF: 0.776

Gnomad4 FIN exome AF: 0.831

Gnomad4 NFE exome AF: 0.789

Gnomad4 OTH exome AF: 0.774

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

Gnomad4 AFR AF: 0.642

Gnomad4 AMR AF: 0.769

Gnomad4 ASJ AF: 0.754

Gnomad4 EAS AF: 0.864

Gnomad4 SAS AF: 0.794

Gnomad4 FIN AF: 0.838

Gnomad4 NFE AF: 0.789

Gnomad4 OTH AF: 0.755

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

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

May 04, 2021

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

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;.;T
Eigen	Benign	-1.7
Eigen_PC	Benign	-1.6
FATHMM_MKL	Benign	0.00044	N
LIST_S2	Benign	0.097	.;T;T
MetaRNN	Benign	8.1e-7	T;T;T
MetaSVM	Benign	-0.96	T
MutationAssessor	Benign	-0.69	N;.;N
PrimateAI	Uncertain	0.69	T
PROVEAN	Benign	0.37	N;N;N
REVEL	Benign	0.076
Sift	Benign	1.0	T;T;T
Sift4G	Benign	0.91	T;T;T
Polyphen		0.0	B;.;B
Vest4		0.026
MPC		0.47
ClinPred		0.00016	T
GERP RS		0.18
Varity_R		0.039
gMVP		0.11

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