rs6488297

Positions:

• chr12-10513426-A-C
• chr12-10513426-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000322446.3(EIF2S3B):​c.1308+6216A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.799 in 152,154 control chromosomes in the GnomAD database, including 49,180 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.80 (49180 hom., cov: 33)
• Consequence: EIF2S3B ENST00000322446.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0120

Genes affected

EIF2S3B (HGNC:43863): (eukaryotic translation initiation factor 2 subunit gamma B) Predicted to enable translation initiation factor activity. Predicted to contribute to tRNA binding activity. Predicted to be involved in formation of translation preinitiation complex and positive regulation of translational fidelity. Predicted to be part of eukaryotic translation initiation factor 2 complex. Predicted to be active in cytosol. [provided by Alliance of Genome Resources, Apr 2022]

LOC105369657 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.0).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.914 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LOC105369657	XR_931355.4	n.442+7216T>G		intron_variant, non_coding_transcript_variant
EIF2S3B	NM_001357731.1	c.1308+6216A>C		intron_variant			NP_001344660.1
LOC105369657	XR_001749003.3	n.442+7216T>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
EIF2S3B	ENST00000322446.3	c.1308+6216A>C		intron_variant		1		ENSP00000323063

Frequencies

GnomAD3 genomes AF: 0.800 AC: 121583 AN: 152038 Hom.: 49159 Cov.: 33

Gnomad AFR AF: 0.666

Gnomad AMI AF: 0.784

Gnomad AMR AF: 0.866

Gnomad ASJ AF: 0.868

Gnomad EAS AF: 0.937

Gnomad SAS AF: 0.860

Gnomad FIN AF: 0.900

Gnomad MID AF: 0.782

Gnomad NFE AF: 0.832

Gnomad OTH AF: 0.813

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.799 AC: 121643 AN: 152154 Hom.: 49180 Cov.: 33 AF XY: 0.804 AC XY: 59796 AN XY: 74388

Gnomad4 AFR AF: 0.666

Gnomad4 AMR AF: 0.866

Gnomad4 ASJ AF: 0.868

Gnomad4 EAS AF: 0.936

Gnomad4 SAS AF: 0.859

Gnomad4 FIN AF: 0.900

Gnomad4 NFE AF: 0.832

Gnomad4 OTH AF: 0.815

Alfa AF: 0.833 Hom.: 102910

Bravo AF: 0.793

Asia WGS AF: 0.884 AC: 3070 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	3.3
DANN	Benign	0.55

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs6488297; hg19: chr12-10666025;