chr1-149845941-T-C

Variant names:

• chr1-149845941-T-C
• rs1046332
• ENST00000564237.2:n.4997A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000564237.2(ENSG00000290792):​n.4997A>G variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0499 in 152,260 control chromosomes in the GnomAD database, including 252 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.050 (252 hom., cov: 32)
  • Exomes 𝑓: 0.50 (0 hom.)
• Consequence: ENSG00000290792 ENST00000564237.2 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.547
• Publications: 11 publications found

Genes affected

ENSG00000290792 (HGNC:):

H4C15 (HGNC:29607): (H4 clustered histone 15) 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 encodes a replication-dependent histone that is a member of the histone H4 family. Some transcripts from this gene lack polyA tails; instead, they contain a palindromic termination element. This gene is found in a histone cluster on chromosome 1. This gene is one of four histone genes in the cluster that are duplicated; this record represents the telomeric copy. [provided by RefSeq, May 2020]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0769 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000564237.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
There are no transcript annotations for this variant.

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ENSG00000290792	ENST00000564237.2	TSL:6	n.4997A>G		non_coding_transcript_exon	Exon 1 of 1
	ENSG00000290791	ENST00000608318.3	TSL:6	n.3784T>C		non_coding_transcript_exon	Exon 1 of 1
	ENSG00000290791	ENST00000779565.1		n.460-614T>C		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.0499 AC: 7595 AN: 152140 Hom.: 252 Cov.: 32

Gnomad AFR AF: 0.0138

Gnomad AMI AF: 0.0362

Gnomad AMR AF: 0.0346

Gnomad ASJ AF: 0.0723

Gnomad EAS AF: 0.000192

Gnomad SAS AF: 0.00932

Gnomad FIN AF: 0.0671

Gnomad MID AF: 0.0253

Gnomad NFE AF: 0.0786

Gnomad OTH AF: 0.0468

GnomAD4 exome AF: 0.500 AC: 1 AN: 2 Hom.: 0 Cov.: 0 AF XY: 0.500 AC XY: 1 AN XY: 2

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AF: 0.500 AC: 1 AN: 2

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AC: 0 AN: 0

Other (OTH) AC: 0 AN: 0

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome AF: 0.0499 AC: 7595 AN: 152258 Hom.: 252 Cov.: 32 AF XY: 0.0479 AC XY: 3566 AN XY: 74436

African (AFR) AF: 0.0138 AC: 572 AN: 41550

American (AMR) AF: 0.0345 AC: 527 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.0723 AC: 251 AN: 3470

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5190

South Asian (SAS) AF: 0.00974 AC: 47 AN: 4824

European-Finnish (FIN) AF: 0.0671 AC: 711 AN: 10598

Middle Eastern (MID) AF: 0.0238 AC: 7 AN: 294

European-Non Finnish (NFE) AF: 0.0786 AC: 5348 AN: 68012

Other (OTH) AF: 0.0464 AC: 98 AN: 2114

Alfa AF: 0.0632 Hom.: 208

Bravo AF: 0.0465

Asia WGS AF: 0.00635 AC: 24 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	3.4
DANN	Benign	0.70
PhyloP100		-0.55

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs1046332; hg19: chr1-149817508;