chr6-27139614-C-A

Variant names:

• chr6-27139614-C-A
• rs61742445
• NM_003495.3:c.306C>A

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 2P and 3B. PM2 BP4_Moderate BP7

The NM_003495.3(H4C9):​c.306C>A​(p.Gly102Gly) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000206 in 1,455,028 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. G102G) has been classified as Benign.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: H4C9 NM_003495.3 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.467
• Publications: 7 publications found

Genes affected

H4C9 (HGNC:4793): (H4 clustered histone 9) 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 histone microcluster on chromosome 6p21.33. [provided by RefSeq, Aug 2015]

H2BC12 (HGNC:13954): (H2B 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 encodes a replication-dependent histone that is a member of the histone H2B family. The protein encoded is an antimicrobial protein with antibacterial and antifungal activity. Two transcripts that encode the same protein have been identified for this gene, which is found in the histone microcluster on chromosome 6p21.33. [provided by RefSeq, Aug 2015]

ACMG classification

Our verdict: Likely_benign. The variant received -1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.44).
• BP7: Synonymous conserved (PhyloP=-0.467 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003495.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	H4C9	NM_003495.3	MANE Select	c.306C>A	p.Gly102Gly	synonymous	Exon 1 of 1	NP_003486.1
	H2BC12	NM_080593.2		c.*10-933G>T		intron	N/A	NP_542160.1	O60814

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	H4C9	ENST00000615353.2	TSL:6 MANE Select	c.306C>A	p.Gly102Gly	synonymous	Exon 1 of 1	ENSP00000481486.1	P62805
	H4C9	ENST00000715894.1		c.306C>A	p.Gly102Gly	synonymous	Exon 1 of 1	ENSP00000520530.1	P62805
	H2BC12	ENST00000715895.1		c.*10-933G>T		intron	N/A	ENSP00000520531.1	O60814

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000206 AC: 3 AN: 1455028 Hom.: 0 Cov.: 30 AF XY: 0.00000276 AC XY: 2 AN XY: 723364

African (AFR) AF: 0.00 AC: 0 AN: 33240

American (AMR) AF: 0.00 AC: 0 AN: 43818

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25534

East Asian (EAS) AF: 0.00 AC: 0 AN: 39646

South Asian (SAS) AF: 0.00 AC: 0 AN: 85422

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53090

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5688

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1108566

Other (OTH) AF: 0.0000500 AC: 3 AN: 60024

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 8

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.44
CADD	Benign	6.4
DANN	Benign	0.83
PhyloP100		-0.47
PromoterAI		0.023	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7

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

Other links and lift over

dbSNP: rs61742445; hg19: chr6-27107393;