6-26240671-C-T

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_StrongBP6_ModerateBP7BS2

The NM_003540.4(H4C6):​c.246C>T​(p.Val82Val) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000331 in 1,612,128 control chromosomes in the GnomAD database, including 4 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0018 ( 1 hom., cov: 33)
Exomes 𝑓: 0.00018 ( 3 hom. )

Consequence

H4C6
NM_003540.4 synonymous

Scores

2

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.267
Variant links:
Genes affected
H4C6 (HGNC:4783): (H4 clustered histone 6) Histones are basic nuclear proteins that are responsible for the nucleosome structure of the chromosomal fiber in eukaryotes. Two molecules of each of the four core histones (H2A, H2B, H3, and H4) form an octamer, around which approximately 146 bp of DNA is wrapped in repeating units, called nucleosomes. The linker histone, H1, interacts with linker DNA between nucleosomes and functions in the compaction of chromatin into higher order structures. This gene is intronless and encodes a replication-dependent histone that is a member of the histone H4 family. Transcripts from this gene lack polyA tails but instead contain a palindromic termination element. This gene is found in the large histone gene cluster on chromosome 6. [provided by RefSeq, Aug 2015]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -11 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.52).
BP6
Variant 6-26240671-C-T is Benign according to our data. Variant chr6-26240671-C-T is described in ClinVar as [Benign]. Clinvar id is 719489.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
Synonymous conserved (PhyloP=0.267 with no splicing effect.
BS2
High Homozygotes in GnomAdExome4 at 3 gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
H4C6NM_003540.4 linkc.246C>T p.Val82Val synonymous_variant Exon 1 of 1 ENST00000244537.6 NP_003531.1 P62805B2R4R0

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
H4C6ENST00000244537.6 linkc.246C>T p.Val82Val synonymous_variant Exon 1 of 1 6 NM_003540.4 ENSP00000244537.6 P62805
ENSG00000291336ENST00000707189.1 linkn.999+116500C>T intron_variant Intron 1 of 1
ENSG00000291338ENST00000707191.1 linkn.1000+82550C>T intron_variant Intron 1 of 1

Frequencies

GnomAD3 genomes
AF:
0.00179
AC:
272
AN:
152242
Hom.:
1
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.00603
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00118
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000588
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.000426
AC:
106
AN:
248660
Hom.:
0
AF XY:
0.000320
AC XY:
43
AN XY:
134284
show subpopulations
Gnomad AFR exome
AF:
0.00493
Gnomad AMR exome
AF:
0.000464
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.0000991
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000447
Gnomad OTH exome
AF:
0.000331
GnomAD4 exome
AF:
0.000177
AC:
258
AN:
1459770
Hom.:
3
Cov.:
32
AF XY:
0.000147
AC XY:
107
AN XY:
726114
show subpopulations
Gnomad4 AFR exome
AF:
0.00502
Gnomad4 AMR exome
AF:
0.000493
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.0000252
Gnomad4 SAS exome
AF:
0.0000931
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000243
Gnomad4 OTH exome
AF:
0.000514
GnomAD4 genome
AF:
0.00180
AC:
275
AN:
152358
Hom.:
1
Cov.:
33
AF XY:
0.00177
AC XY:
132
AN XY:
74494
show subpopulations
Gnomad4 AFR
AF:
0.00608
Gnomad4 AMR
AF:
0.00118
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000588
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.000888
Hom.:
0
Bravo
AF:
0.00196
Asia WGS
AF:
0.000289
AC:
1
AN:
3478

ClinVar

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

Submissions by phenotype

not provided Benign:1
Apr 24, 2018
Labcorp Genetics (formerly Invitae), Labcorp
Significance: Benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing

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Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.52
CADD
Benign
7.6
DANN
Benign
0.87

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.050
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: rs115414626; hg19: chr6-26240899; API