rs150880

chr7-74176576-G-A

Variant summary

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

The NM_022170.2(EIF4H):c.59+2134G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.938 in 152,290 control chromosomes in the GnomAD database, including 66,982 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 0.94 (66982 hom., cov: 33)
• Consequence: EIF4H NM_022170.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.693

Genes affected

EIF4H (HGNC:12741): (eukaryotic translation initiation factor 4H) This gene encodes one of the translation initiation factors, which functions to stimulate the initiation of protein synthesis at the level of mRNA utilization. This gene is deleted in Williams syndrome, a multisystem developmental disorder caused by the deletion of contiguous genes at 7q11.23. Alternative splicing of this gene generates 2 transcript variants. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.948 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
EIF4H	NM_022170.2	c.59+2134G>A		intron_variant		ENST00000265753.13
EIF4H	NM_031992.2	c.59+2134G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
EIF4H	ENST00000265753.13	c.59+2134G>A		intron_variant		2	NM_022170.2

Frequencies

GnomAD3 genomes AF: 0.938 AC: 142690 AN: 152172 Hom.: 66942 Cov.: 33

Gnomad AFR AF: 0.915

Gnomad AMI AF: 0.996

Gnomad AMR AF: 0.945

Gnomad ASJ AF: 0.968

Gnomad EAS AF: 0.912

Gnomad SAS AF: 0.922

Gnomad FIN AF: 0.911

Gnomad MID AF: 0.943

Gnomad NFE AF: 0.954

Gnomad OTH AF: 0.951

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

GnomAD4 genome AF: 0.938 AC: 142785 AN: 152290 Hom.: 66982 Cov.: 33 AF XY: 0.934 AC XY: 69576 AN XY: 74460

Gnomad4 AFR AF: 0.915

Gnomad4 AMR AF: 0.945

Gnomad4 ASJ AF: 0.968

Gnomad4 EAS AF: 0.912

Gnomad4 SAS AF: 0.922

Gnomad4 FIN AF: 0.911

Gnomad4 NFE AF: 0.954

Gnomad4 OTH AF: 0.951

Alfa AF: 0.938 Hom.: 11781

Bravo AF: 0.940

Asia WGS AF: 0.892 AC: 3103 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
Cadd	Benign	0.45
Dann	Benign	0.47

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: rs150880; hg19: chr7-73590906;