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GeneBe

3-15434411-G-A

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_StrongBP6_ModerateBP7BA1

The NM_033083.7(EAF1):c.399G>A(p.Thr133=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00359 in 1,614,156 control chromosomes in the GnomAD database, including 165 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.019 ( 85 hom., cov: 32)
Exomes 𝑓: 0.0020 ( 80 hom. )

Consequence

EAF1
NM_033083.7 synonymous

Scores

2

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -3.49
Variant links:
Genes affected
EAF1 (HGNC:20907): (ELL associated factor 1) Enables transcription elongation regulator activity. Involved in regulation of transcription elongation from RNA polymerase II promoter. Located in intercellular bridge and nuclear body. Part of transcription elongation factor complex. [provided by Alliance of Genome Resources, Apr 2022]
METTL6 (HGNC:28343): (methyltransferase 6, tRNA N3-cytidine) Enables enzyme binding activity. Involved in tRNA methylation. [provided by Alliance of Genome Resources, Apr 2022]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -15 ACMG points.

BP4
?
    BP4 - Multiple lines of computational evidence suggest no impact on gene or gene product (conservation, evolutionary, splicing impact, etc.)
Computational evidence support a benign effect (BayesDel_noAF=-0.77).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
Variant 3-15434411-G-A is Benign according to our data. Variant chr3-15434411-G-A is described in ClinVar as [Benign]. Clinvar id is 787010.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
?
    BP7 - A synonymous (silent) variant for which splicing prediction algorithms predict no impact to the splice consensus sequence nor the creation of a new splice site AND the nucleotide is not highly conserved
Synonymous conserved (PhyloP=-3.49 with no splicing effect.
BA1
?
    BA1 - Allele frequency is >5% in Exome Sequencing Project, 1000 Genomes Project, or Exome Aggregation Consortium
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0607 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
EAF1NM_033083.7 linkuse as main transcriptc.399G>A p.Thr133= synonymous_variant 4/6 ENST00000396842.7
EAF1XM_011534165.2 linkuse as main transcriptc.96G>A p.Thr32= synonymous_variant 3/5
EAF1XM_011534166.2 linkuse as main transcriptc.96G>A p.Thr32= synonymous_variant 3/5

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
EAF1ENST00000396842.7 linkuse as main transcriptc.399G>A p.Thr133= synonymous_variant 4/61 NM_033083.7 P1Q96JC9-1
METTL6ENST00000598878.1 linkuse as main transcriptc.-125+4767C>T intron_variant 5
EAF1ENST00000449565.1 linkuse as main transcriptc.*58G>A 3_prime_UTR_variant, NMD_transcript_variant 3/52

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.0187
AC:
2842
AN:
152148
Hom.:
85
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0629
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.0117
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.000192
Gnomad SAS
AF:
0.000414
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.000250
Gnomad OTH
AF:
0.0186
GnomAD3 exomes
AF:
0.00490
AC:
1231
AN:
251402
Hom.:
35
AF XY:
0.00354
AC XY:
481
AN XY:
135874
show subpopulations
Gnomad AFR exome
AF:
0.0644
Gnomad AMR exome
AF:
0.00408
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.0000544
Gnomad SAS exome
AF:
0.0000980
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.000202
Gnomad OTH exome
AF:
0.00277
GnomAD4 exome
AF:
0.00202
AC:
2946
AN:
1461890
Hom.:
80
Cov.:
30
AF XY:
0.00168
AC XY:
1221
AN XY:
727246
show subpopulations
Gnomad4 AFR exome
AF:
0.0655
Gnomad4 AMR exome
AF:
0.00508
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.000101
Gnomad4 SAS exome
AF:
0.000139
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.000219
Gnomad4 OTH exome
AF:
0.00429
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.0187
AC:
2843
AN:
152266
Hom.:
85
Cov.:
32
AF XY:
0.0184
AC XY:
1373
AN XY:
74450
show subpopulations
Gnomad4 AFR
AF:
0.0627
Gnomad4 AMR
AF:
0.0116
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.000193
Gnomad4 SAS
AF:
0.000207
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.000250
Gnomad4 OTH
AF:
0.0184
Alfa
AF:
0.00986
Hom.:
16
Bravo
AF:
0.0220
Asia WGS
AF:
0.00260
AC:
9
AN:
3478
EpiCase
AF:
0.000218
EpiControl
AF:
0.000237

ClinVar

Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not provided Benign:1
Benign, criteria provided, single submitterclinical testingInvitaeDec 31, 2019- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.77
Cadd
Benign
0.63
Dann
Benign
0.79

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.010
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

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs6772957; hg19: chr3-15475918; API