chr1-41510658-C-T

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6BP7

The NM_024503.5(HIVEP3):​c.7014G>A​(p.Pro2338=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000648 in 1,527,850 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (no stars).

Frequency

Genomes: 𝑓 0.00048 ( 0 hom., cov: 33)
Exomes 𝑓: 0.00067 ( 1 hom. )

Consequence

HIVEP3
NM_024503.5 synonymous

Scores

2

Clinical Significance

Likely benign no assertion criteria provided B:1

Conservation

PhyloP100: 0.585
Variant links:
Genes affected
HIVEP3 (HGNC:13561): (HIVEP zinc finger 3) This gene encodes a member of the human immunodeficiency virus type 1 enhancer-binding protein family. Members of this protein family contain multiple zinc finger and acid-rich (ZAS) domains and serine-threonine rich regions. This protein acts as a transcription factor and is able to regulate nuclear factor kappaB-mediated transcription by binding the kappaB motif in target genes. This protein also binds the recombination signal sequence that flanks the V, D, and J regions of immunoglobulin and T-cell receptors. Alternate splicing results in both coding and non-coding transcript variants. [provided by RefSeq, Sep 2011]

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.75).
BP6
Variant 1-41510658-C-T is Benign according to our data. Variant chr1-41510658-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 3041313.Status of the report is no_assertion_criteria_provided, 0 stars.
BP7
Synonymous conserved (PhyloP=0.585 with no splicing effect.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
HIVEP3NM_024503.5 linkuse as main transcriptc.7014G>A p.Pro2338= synonymous_variant 9/9 ENST00000372583.6 NP_078779.2
HIVEP3NM_001127714.3 linkuse as main transcriptc.7011G>A p.Pro2337= synonymous_variant 8/8 NP_001121186.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
HIVEP3ENST00000372583.6 linkuse as main transcriptc.7014G>A p.Pro2338= synonymous_variant 9/91 NM_024503.5 ENSP00000361664 P5Q5T1R4-1
HIVEP3ENST00000372584.5 linkuse as main transcriptc.7011G>A p.Pro2337= synonymous_variant 8/81 ENSP00000361665 A2Q5T1R4-2
HIVEP3ENST00000643665.1 linkuse as main transcriptc.7011G>A p.Pro2337= synonymous_variant 8/8 ENSP00000494598 A2Q5T1R4-2
HIVEP3ENST00000460604.1 linkuse as main transcriptn.1941G>A non_coding_transcript_exon_variant 5/52

Frequencies

GnomAD3 genomes
AF:
0.000480
AC:
73
AN:
152152
Hom.:
0
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.000193
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.000131
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.000207
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.000882
Gnomad OTH
AF:
0.000956
GnomAD3 exomes
AF:
0.000455
AC:
62
AN:
136398
Hom.:
1
AF XY:
0.000464
AC XY:
34
AN XY:
73218
show subpopulations
Gnomad AFR exome
AF:
0.000280
Gnomad AMR exome
AF:
0.000212
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.0000475
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00102
Gnomad OTH exome
AF:
0.000510
GnomAD4 exome
AF:
0.000667
AC:
917
AN:
1375580
Hom.:
1
Cov.:
34
AF XY:
0.000627
AC XY:
424
AN XY:
675922
show subpopulations
Gnomad4 AFR exome
AF:
0.000288
Gnomad4 AMR exome
AF:
0.000174
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.0000281
Gnomad4 SAS exome
AF:
0.0000387
Gnomad4 FIN exome
AF:
0.0000232
Gnomad4 NFE exome
AF:
0.000807
Gnomad4 OTH exome
AF:
0.000597
GnomAD4 genome
AF:
0.000479
AC:
73
AN:
152270
Hom.:
0
Cov.:
33
AF XY:
0.000416
AC XY:
31
AN XY:
74460
show subpopulations
Gnomad4 AFR
AF:
0.000193
Gnomad4 AMR
AF:
0.000131
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.000207
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.000882
Gnomad4 OTH
AF:
0.000946
Alfa
AF:
0.000171
Hom.:
1
Bravo
AF:
0.000514

ClinVar

Significance: Likely benign
Submissions summary: Benign:1
Revision: no assertion criteria provided
LINK: link

Submissions by phenotype

HIVEP3-related disorder Benign:1
Likely benign, no assertion criteria providedclinical testingPreventionGenetics, part of Exact SciencesFeb 21, 2019This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.75
CADD
Benign
1.2
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

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

Other links and lift over

dbSNP: rs559361161; hg19: chr1-41976329; COSMIC: COSV56017057; API