chr12-53014796-A-G

Variant names:

• chr12-53014796-A-G
• rs7957445
• NM_001417.7:c.14-1677A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001417.7(EIF4B):​c.14-1677A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.603 in 152,202 control chromosomes in the GnomAD database, including 34,316 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 0.60 (34316 hom., cov: 32)
  • Failed GnomAD Quality Control
• Consequence: EIF4B NM_001417.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.78
• Publications: 5 publications found

Genes affected

EIF4B (HGNC:3285): (eukaryotic translation initiation factor 4B) Enables RNA binding activity. Predicted to be involved in eukaryotic translation initiation factor 4F complex assembly and formation of translation preinitiation complex. Located in cytosol. Biomarker of autism spectrum disorder and major depressive disorder. [provided by Alliance of Genome Resources, Apr 2022]

TNS2-AS1 (HGNC:27464): (TNS2 antisense RNA 1)

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.75).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.845 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EIF4B	NM_001417.7	c.14-1677A>G		intron_variant	Intron 1 of 14	ENST00000262056.14	NP_001408.2
EIF4B	NM_001300821.3	c.14-1677A>G		intron_variant	Intron 1 of 14		NP_001287750.1
EIF4B	NM_001330654.2	c.14-1677A>G		intron_variant	Intron 1 of 13		NP_001317583.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
EIF4B	ENST00000262056.14	c.14-1677A>G		intron_variant	Intron 1 of 14	1	NM_001417.7	ENSP00000262056.9

Frequencies

GnomAD3 genomes AF: 0.604 AC: 91784 AN: 152084 Hom.: 34325 Cov.: 32

Gnomad AFR AF: 0.170

Gnomad AMI AF: 0.848

Gnomad AMR AF: 0.624

Gnomad ASJ AF: 0.859

Gnomad EAS AF: 0.296

Gnomad SAS AF: 0.562

Gnomad FIN AF: 0.728

Gnomad MID AF: 0.763

Gnomad NFE AF: 0.851

Gnomad OTH AF: 0.675

GnomAD4 exome Data not reliable, filtered out with message: AC0 AC: 0 AN: 0 Hom.: 0 Cov.: 0 AC XY: 0 AN XY: 0

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AC: 0 AN: 0

Other (OTH) AC: 0 AN: 0

GnomAD4 genome AF: 0.603 AC: 91771 AN: 152202 Hom.: 34316 Cov.: 32 AF XY: 0.595 AC XY: 44275 AN XY: 74422

African (AFR) AF: 0.169 AC: 7020 AN: 41526

American (AMR) AF: 0.624 AC: 9533 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.859 AC: 2981 AN: 3472

East Asian (EAS) AF: 0.296 AC: 1536 AN: 5182

South Asian (SAS) AF: 0.565 AC: 2720 AN: 4818

European-Finnish (FIN) AF: 0.728 AC: 7710 AN: 10592

Middle Eastern (MID) AF: 0.762 AC: 224 AN: 294

European-Non Finnish (NFE) AF: 0.851 AC: 57863 AN: 68008

Other (OTH) AF: 0.667 AC: 1411 AN: 2114

Alfa AF: 0.737 Hom.: 16242

Bravo AF: 0.576

Asia WGS AF: 0.400 AC: 1392 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.75
CADD	Benign	8.4
DANN	Benign	0.88
PhyloP100		1.8
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: rs7957445; hg19: chr12-53408580;