Genetic Variant NM_022170.2:c.607+107A>G (chr7-74194985-A-G) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

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

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.431

Publications

10 publications found

Variant links:

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]

EIF4H links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
EIF4H	NM_022170.2 link	c.607+107A>G		intron_variant	Intron 6 of 6	ENST00000265753.13	NP_071496.1	Q15056-1
EIF4H	NM_031992.2 link	c.547+107A>G		intron_variant	Intron 5 of 5		NP_114381.1	Q15056-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
EIF4H	ENST00000265753.13 link	c.607+107A>G		intron_variant	Intron 6 of 6	2	NM_022170.2	ENSP00000265753.8		Q15056-1

Frequencies

GnomAD3 genomes

AF:

0.0313

AC:

4765

AN:

152226

Hom.:

169

Cov.:

show subpopulations

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.:

AF XY:

0.0272

AC XY:

18031

AN XY:

662172

show subpopulations

African (AFR)

AF:

0.00545

AC:

166

AN:

30436

American (AMR)

AF:

0.111

AC:

3304

AN:

29640

Ashkenazi Jewish (ASJ)

AF:

0.0290

AC:

597

AN:

20584

East Asian (EAS)

AF:

0.136

AC:

5127

AN:

37662

South Asian (SAS)

AF:

0.0417

AC:

2967

AN:

71096

European-Finnish (FIN)

AF:

0.0639

AC:

3098

AN:

48482

Middle Eastern (MID)

AF:

0.0204

AC:

108

AN:

5302

European-Non Finnish (NFE)

AF:

0.0185

AC:

19480

AN:

1055672

Other (OTH)

AF:

0.0322

AC:

1801

AN:

55962

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1821

3642

5464

7285

9106

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

856

1712

2568

3424

4280

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0314

AC:

4781

AN:

152344

Hom.:

175

Cov.:

AF XY:

0.0354

AC XY:

2637

AN XY:

74494

show subpopulations

African (AFR)

AF:

0.00628

AC:

261

AN:

41576

American (AMR)

AF:

0.0777

AC:

1190

AN:

15308

Ashkenazi Jewish (ASJ)

AF:

0.0268

AC:

AN:

3472

East Asian (EAS)

AF:

0.159

AC:

827

AN:

5188

South Asian (SAS)

AF:

0.0422

AC:

204

AN:

4834

European-Finnish (FIN)

AF:

0.0682

AC:

724

AN:

10610

Middle Eastern (MID)

AF:

0.0272

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0205

AC:

1397

AN:

68034

Other (OTH)

AF:

0.0350

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

237

474

712

949

1186

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

116

174

232

290

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0290

Hom.:

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

(source)

DANN

Benign

0.58

PhyloP100

-0.43

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over