6-27831480-A-T

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_003541.3(H4C12):​c.48T>A​(p.Ala16Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0419 in 1,526,882 control chromosomes in the GnomAD database, including 1,248 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.033 ( 112 hom., cov: 32)
Exomes 𝑓: 0.043 ( 1136 hom. )

Consequence

H4C12
NM_003541.3 synonymous

Scores

2

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.439
Variant links:
Genes affected
H4C12 (HGNC:4784): (H4 clustered histone 12) 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 small histone gene cluster on chromosome 6p22-p21.3. [provided by RefSeq, Aug 2015]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.75).
BP6
Variant 6-27831480-A-T is Benign according to our data. Variant chr6-27831480-A-T is described in ClinVar as [Likely_benign]. Clinvar id is 774643.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
Synonymous conserved (PhyloP=-0.439 with no splicing effect.
BA1
GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.0641 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
H4C12NM_003541.3 linkc.48T>A p.Ala16Ala synonymous_variant Exon 1 of 1 ENST00000611927.2 NP_003532.1 P62805B2R4R0

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
H4C12ENST00000611927.2 linkc.48T>A p.Ala16Ala synonymous_variant Exon 1 of 1 6 NM_003541.3 ENSP00000479794.2 P62805

Frequencies

GnomAD3 genomes
AF:
0.0335
AC:
5101
AN:
152178
Hom.:
113
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00794
Gnomad AMI
AF:
0.0537
Gnomad AMR
AF:
0.0201
Gnomad ASJ
AF:
0.0268
Gnomad EAS
AF:
0.0221
Gnomad SAS
AF:
0.0702
Gnomad FIN
AF:
0.0624
Gnomad MID
AF:
0.0190
Gnomad NFE
AF:
0.0462
Gnomad OTH
AF:
0.0297
GnomAD3 exomes
AF:
0.0394
AC:
6684
AN:
169720
Hom.:
188
AF XY:
0.0418
AC XY:
3772
AN XY:
90168
show subpopulations
Gnomad AFR exome
AF:
0.00669
Gnomad AMR exome
AF:
0.0154
Gnomad ASJ exome
AF:
0.0274
Gnomad EAS exome
AF:
0.0184
Gnomad SAS exome
AF:
0.0771
Gnomad FIN exome
AF:
0.0645
Gnomad NFE exome
AF:
0.0437
Gnomad OTH exome
AF:
0.0404
GnomAD4 exome
AF:
0.0429
AC:
58945
AN:
1374586
Hom.:
1136
Cov.:
34
AF XY:
0.0440
AC XY:
29713
AN XY:
675500
show subpopulations
Gnomad4 AFR exome
AF:
0.00557
Gnomad4 AMR exome
AF:
0.0160
Gnomad4 ASJ exome
AF:
0.0273
Gnomad4 EAS exome
AF:
0.00899
Gnomad4 SAS exome
AF:
0.0755
Gnomad4 FIN exome
AF:
0.0654
Gnomad4 NFE exome
AF:
0.0433
Gnomad4 OTH exome
AF:
0.0389
GnomAD4 genome
AF:
0.0335
AC:
5096
AN:
152296
Hom.:
112
Cov.:
32
AF XY:
0.0346
AC XY:
2573
AN XY:
74464
show subpopulations
Gnomad4 AFR
AF:
0.00791
Gnomad4 AMR
AF:
0.0201
Gnomad4 ASJ
AF:
0.0268
Gnomad4 EAS
AF:
0.0214
Gnomad4 SAS
AF:
0.0702
Gnomad4 FIN
AF:
0.0624
Gnomad4 NFE
AF:
0.0462
Gnomad4 OTH
AF:
0.0294
Alfa
AF:
0.0370
Hom.:
15
Bravo
AF:
0.0279

ClinVar

Significance: Likely benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

not provided Benign:2
Jun 23, 2018
Labcorp Genetics (formerly Invitae), Labcorp
Significance: Likely benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing

- -

-
Breakthrough Genomics, Breakthrough Genomics
Significance: Likely benign
Review Status: criteria provided, single submitter
Collection Method: not provided

- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.75
CADD
Benign
5.1
DANN
Benign
0.51

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: rs41269273; hg19: chr6-27799258; API