Genetic Variant H3C2:p.Asn109Asn (chr6-26031734-G-A) – ACMG Classification: Benign (-13 pts)

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP6BA1

The NM_003537.4(H3C2):c.327C>T(p.Asn109Asn) variant causes a synonymous change. The variant allele was found at a frequency of 0.00935 in 1,614,190 control chromosomes in the GnomAD database, including 416 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 0.031 ( 216 hom., cov: 33)

Exomes 𝑓: 0.0071 ( 200 hom. )

Consequence

H3C2
NM_003537.4 synonymous

Scores

Clinical Significance

Likely benign no assertion criteria provided B:1

Conservation

PhyloP100: 5.54

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 -13 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.59).

BP6

Variant 6-26031734-G-A is Benign according to our data. Variant chr6-26031734-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 873165.Status of the report is no_assertion_criteria_provided, 0 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0924 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
H3C2	NM_003537.4 link	c.327C>T	p.Asn109Asn	synonymous_variant	Exon 1 of 1	ENST00000621411.3	NP_003528.1	P68431

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
H3C2	ENST00000621411.3 link	c.327C>T	p.Asn109Asn	synonymous_variant	Exon 1 of 1	6	NM_003537.4	ENSP00000484841.2		P68431

Frequencies

GnomAD3 genomes

AF:

0.0309

AC:

4710

AN:

152190

Hom.:

216

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0950

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0209

Gnomad ASJ

AF:

0.00461

Gnomad EAS

AF:

0.00116

Gnomad SAS

AF:

0.00455

Gnomad FIN

AF:

0.0000942

Gnomad MID

AF:

0.0253

Gnomad NFE

AF:

0.00509

Gnomad OTH

AF:

0.0253

GnomAD3 exomes

AF:

0.0113

AC:

2837

AN:

251484

Hom.:

AF XY:

0.00927

AC XY:

1260

AN XY:

135916

show subpopulations

Gnomad AFR exome

AF:

0.0981

Gnomad AMR exome

AF:

0.0123

Gnomad ASJ exome

AF:

0.00377

Gnomad EAS exome

AF:

0.00261

Gnomad SAS exome

AF:

0.00474

Gnomad FIN exome

AF:

0.000185

Gnomad NFE exome

AF:

0.00461

Gnomad OTH exome

AF:

0.00912

GnomAD4 exome

AF:

0.00710

AC:

10377

AN:

1461882

Hom.:

200

Cov.:

AF XY:

0.00660

AC XY:

4800

AN XY:

727244

show subpopulations

Gnomad4 AFR exome

AF:

0.0984

Gnomad4 AMR exome

AF:

0.0135

Gnomad4 ASJ exome

AF:

0.00413

Gnomad4 EAS exome

AF:

0.00171

Gnomad4 SAS exome

AF:

0.00539

Gnomad4 FIN exome

AF:

0.000468

Gnomad4 NFE exome

AF:

0.00461

Gnomad4 OTH exome

AF:

0.0103

GnomAD4 genome

AF:

0.0310

AC:

4714

AN:

152308

Hom.:

216

Cov.:

AF XY:

0.0296

AC XY:

2207

AN XY:

74486

show subpopulations

Gnomad4 AFR

AF:

0.0949

Gnomad4 AMR

AF:

0.0208

Gnomad4 ASJ

AF:

0.00461

Gnomad4 EAS

AF:

0.00116

Gnomad4 SAS

AF:

0.00456

Gnomad4 FIN

AF:

0.0000942

Gnomad4 NFE

AF:

0.00509

Gnomad4 OTH

AF:

0.0250

Alfa

AF:

0.0161

Hom.:

Bravo

AF:

0.0371

Asia WGS

AF:

0.00779

AC:

AN:

3478

EpiCase

AF:

0.00453

EpiControl

AF:

0.00492

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

Squamous cell lung carcinoma

Benign:1

May 05, 2020

Faculté Pluridciplinaire Nador, Université Mohamed Premier

Significance: Likely benign

Review Status: no assertion criteria provided

Collection Method: clinical testing;in vivo

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.59

CADD

Benign

4.6

DANN

Benign

0.91

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

2.7

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.

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