rs17146094

Positions:

• chr7-74194985-A-G

Variant summary

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

The NM_022170.2(EIF4H):​c.607+107A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0275 in 1,507,180 control chromosomes in the GnomAD database, including 1,179 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 0.031 (175 hom., cov: 32)
  • Exomes 𝑓: 0.027 (1004 hom.)
• Consequence: EIF4H NM_022170.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.431

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=-0.86).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.15 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
EIF4H	NM_022170.2	c.607+107A>G		intron_variant		ENST00000265753.13
EIF4H	NM_031992.2	c.547+107A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
EIF4H	ENST00000265753.13	c.607+107A>G		intron_variant		2	NM_022170.2

Frequencies

GnomAD3 genomes AF: 0.0313 AC: 4765 AN: 152226 Hom.: 169 Cov.: 32

Gnomad AFR AF: 0.00625

Gnomad AMI AF: 0.00329

Gnomad AMR AF: 0.0770

Gnomad ASJ AF: 0.0268

Gnomad EAS AF: 0.159

Gnomad SAS AF: 0.0420

Gnomad FIN AF: 0.0682

Gnomad MID AF: 0.0285

Gnomad NFE AF: 0.0205

Gnomad OTH AF: 0.0349

GnomAD4 exome AF: 0.0270 AC: 36648 AN: 1354836 Hom.: 1004 Cov.: 28 AF XY: 0.0272 AC XY: 18031 AN XY: 662172

Gnomad4 AFR exome AF: 0.00545

Gnomad4 AMR exome AF: 0.111

Gnomad4 ASJ exome AF: 0.0290

Gnomad4 EAS exome AF: 0.136

Gnomad4 SAS exome AF: 0.0417

Gnomad4 FIN exome AF: 0.0639

Gnomad4 NFE exome AF: 0.0185

Gnomad4 OTH exome AF: 0.0322

GnomAD4 genome AF: 0.0314 AC: 4781 AN: 152344 Hom.: 175 Cov.: 32 AF XY: 0.0354 AC XY: 2637 AN XY: 74494

Gnomad4 AFR AF: 0.00628

Gnomad4 AMR AF: 0.0777

Gnomad4 ASJ AF: 0.0268

Gnomad4 EAS AF: 0.159

Gnomad4 SAS AF: 0.0422

Gnomad4 FIN AF: 0.0682

Gnomad4 NFE AF: 0.0205

Gnomad4 OTH AF: 0.0350

Alfa AF: 0.0319 Hom.: 29

Bravo AF: 0.0328

Asia WGS AF: 0.0840 AC: 292 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	1.7
DANN	Benign	0.58

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: rs17146094; hg19: chr7-73609315; COSMIC: COSV56082751; COSMIC: COSV56082751;