Variant 6-26031640-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_003537.4(H3C2):c.*10C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.708 in 1,609,084 control chromosomes in the GnomAD database, including 407,089 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (no stars).

Frequency

Genomes: 𝑓 0.75 ( 44213 hom., cov: 34)

Exomes 𝑓: 0.70 ( 362876 hom. )

Consequence

H3C2
NM_003537.4 3_prime_UTR

Scores

Clinical Significance

Uncertain significance no assertion criteria provided U:1

Conservation

PhyloP100: -2.19

Variant links:

Genes affected

H3C2 (HGNC:4776): (H3 clustered histone 2) Histones are basic nuclear proteins that are responsible for the nucleosome structure of the chromosomal fiber in eukaryotes. This structure consists of approximately 146 bp of DNA wrapped around a nucleosome, an octamer composed of pairs of each of the four core histones (H2A, H2B, H3, and H4). The chromatin fiber is further compacted through the interaction of a linker histone, H1, with the DNA between the nucleosomes to form higher order chromatin structures. This gene is intronless and encodes a replication-dependent histone that is a member of the histone H3 family. Transcripts from this gene lack polyA tails; instead, they contain a palindromic termination element. This gene is found in the large histone gene cluster on chromosome 6p22-p21.3. [provided by RefSeq, Aug 2015]

H3C2 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.89).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.906 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
H3C2	NM_003537.4 linkuse as main transcript	c.*10C>T		3_prime_UTR_variant	1/1	ENST00000621411.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
H3C2	ENST00000621411.3 linkuse as main transcript	c.*10C>T		3_prime_UTR_variant	1/1		NM_003537.4	P1

Frequencies

GnomAD3 genomes

AF:

0.755

AC:

114799

AN:

152128

Hom.:

44171

Cov.:

show subpopulations

Gnomad AFR

AF:

0.913

Gnomad AMI

AF:

0.635

Gnomad AMR

AF:

0.712

Gnomad ASJ

AF:

0.713

Gnomad EAS

AF:

0.860

Gnomad SAS

AF:

0.663

Gnomad FIN

AF:

0.677

Gnomad MID

AF:

0.696

Gnomad NFE

AF:

0.681

Gnomad OTH

AF:

0.773

GnomAD3 exomes

AF:

0.704

AC:

174072

AN:

247312

Hom.:

62208

AF XY:

0.699

AC XY:

93449

AN XY:

133754

show subpopulations

Gnomad AFR exome

AF:

0.917

Gnomad AMR exome

AF:

0.670

Gnomad ASJ exome

AF:

0.726

Gnomad EAS exome

AF:

0.868

Gnomad SAS exome

AF:

0.666

Gnomad FIN exome

AF:

0.668

Gnomad NFE exome

AF:

0.672

Gnomad OTH exome

AF:

0.696

GnomAD4 exome

AF:

0.703

AC:

1024794

AN:

1456838

Hom.:

362876

Cov.:

AF XY:

0.701

AC XY:

508171

AN XY:

724874

show subpopulations

Gnomad4 AFR exome

AF:

0.926

Gnomad4 AMR exome

AF:

0.675

Gnomad4 ASJ exome

AF:

0.727

Gnomad4 EAS exome

AF:

0.887

Gnomad4 SAS exome

AF:

0.670

Gnomad4 FIN exome

AF:

0.671

Gnomad4 NFE exome

AF:

0.694

Gnomad4 OTH exome

AF:

0.722

GnomAD4 genome

AF:

0.755

AC:

114896

AN:

152246

Hom.:

44213

Cov.:

AF XY:

0.753

AC XY:

56067

AN XY:

74432

show subpopulations

Gnomad4 AFR

AF:

0.914

Gnomad4 AMR

AF:

0.712

Gnomad4 ASJ

AF:

0.713

Gnomad4 EAS

AF:

0.859

Gnomad4 SAS

AF:

0.662

Gnomad4 FIN

AF:

0.677

Gnomad4 NFE

AF:

0.681

Gnomad4 OTH

AF:

0.769

Alfa

AF:

0.691

Hom.:

49858

Bravo

AF:

0.767

Asia WGS

AF:

0.738

AC:

2569

AN:

3478

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

Squamous cell lung carcinoma

Uncertain:1

Uncertain significance, no assertion criteria provided

clinical testing;in vivo

Faculté Pluridciplinaire Nador, Université Mohamed Premier

May 05, 2020

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.89

CADD

Benign

0.44

DANN

Benign

0.77

Splicing

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over